Home Remedies for Hyperglycemia

Blood Sugar Miracle

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Blood Sugar Miracle Overview

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Can hypoglycaemia be avoided by constant high blood glucose levels

Having persistently high blood glucose levels will avoid hypoglycaemia, but unfortunately it dramatically increases the risk ofdeveloping the long-term complications of diabetes. Maintaining the balance between risky hyperglycaemia and troublesome hypoglycaemia can be very difficult for patients on insulin, but is much easier these days with the different preparations and injection devices available. If you are having troublesome hypo attacks, followed by high blood glucose levels, please

Blood Glucose and Related Blood Sugar Tests

Glucose, a simple sugar, is the main blood carbohydrate and a major source of energy for all cells. The fasting blood sugar (FBS), postprandial blood sugar (PPBS), and the glucose tolerance test (GTT), or standard oral glucose tolerance test (SOGTT), are three of the most frequently performed blood sugar tests and are used to determine the level of glucose in the blood. Variations in blood glucose levels are broadly categorized as hyperglycemia, or increased blood sugar levels, and hypoglycemia, or decreased blood sugar levels. Variations from Normal. An increase in blood glucose, hyperglycemia, usually indicates diabetes. Myocardial infarction, meningitis, or encephalitis, all of which produce acute stress in bodily processes, may also cause an elevated blood glucose level. Other conditions associated with hyperglycemia include an increased secretion of glucocorticoids from the adrenal glands as seen in Cushing's disease, pituitary and pancreatic adenomas, pancreatitis,...

Proglucagon Gene Products

GLP-1 is an incretin mimetic that has been found to upregulate insulin gene expression (92). It promotes meal-induced insulin secretion, resulting in reduced blood glucose level. Lower blood glucose level is also achieved via a GLP-1 inhibitory effect on glucagon secretion and reduced gastric emptying. The latter slows the rate of nutrient transit to the small intestine, leading to decreased glycemic excursion after meal ingestion (91,93). Both intravenous and subcutaneous infusions have been shown to normalize blood glucose levels in poorly controlled diabetics. HbA1c was shown to be reduced by 1.3 over a 6-wk period of subcutaneous infusion of GLP-1 in addition to a 2-kg weight loss (94). GLP-1 also stimulates B-cell proliferation and promotes islet cell neogenesis (95). This is thought to be mediated through GLP-1R.

Diet and medical problems Diabetes

Protein, while an insulin stimulant, does not increase blood sugar in the amounts usually eaten. Hyperglycemia can contribute to increased protein turnover. However, since most adults eat much more protein than is required, there is no need for diabetics to increase protein intake beyond usual levels (evidence level B). For those with diabetic nephropathy, reduction of protein intake to 0.8 g per kilogram of body weight may slow the progression of renal disease (evidence level C).

What are the physical consequences

Complications are conditions that arise as a result of having diabetes. Some are short term, for example hypoglycaemia (low blood glucose), hyperglycaemia (high blood glucose) and ketoacidosis (very high blood glucose). Others are more long term and develop gradually over time and include heart disease, high blood pressure, damage to the kidneys, and eye and nerve damage.

Coronary Heart Disease in Vegetarian South Asians

South Asian migrants from the Indian subcontinent (Bangladesh, India, and Pakistan) have higher mortality from CHD than other ethnic groups living in the new host country.84 Reliable population-based CHD mortality data are not available from South Asia, but mortality is probably low in rural areas and high in urban areas.84 Many South Asians are vegetarians, which might suggest that this type of vegetarian diet does not reduce the risk for CHD. However, South Asians differ from other ethnic groups, both in many aspects of lifestyle and also genetically, and a case-control study of risk factors for CHD (specifically acute myocardial infarction) in Bangalore, India, did observe a 45 reduction in risk in vegetarians, which was partly explained by their lower blood glucose concentration and lower waist to hip ratio.85

Growth Hormone GH Somatotropin Somatotropic Hormone STH

Decreased growth hormone levels during childhood can result in the premature closure of epiphyseal disks, which in turn causes a cessation of growth known as dwarfism. Other conditions related to decreased growth hormone levels are pituitary insufficiency, hyperglycemia, and failure to thrive.

The Troglitazone in the Prevention of Diabetes Study

Recent data from the Diabetes Epidemiology Collaborative Analysis of Diagnostic Criteria in Europe trial indicate that as many as one-third of diabetic patients can be missed by simply using a fasting blood sugar, because postprandial glucose elevations precede the development of fasting hyperglycemia. Therefore, the following patient types should be considered for diabetic screening with postprandial sugars

What is hyperglycaemia

Hyperglycaemia, or high blood sugar, is arbitrarily defined as a glucose level of > 12 mmol l. Hyperglycaemia may come on suddenly, or its onset may be more gradual, but in any case high blood sugar is not to be taken lightly. In the short-term, elevated blood sugar levels may cause diabetic ketoacidosis, generally in people with type 1 diabetes. Prolonged hyperglycaemia, lasting over the course of several years, can lead to diabetic complications such as damage to blood vessels and nerves throughout the body.

Malnutritionassociated Diabetes

The fasting plasma glucose test is the most popular choice and is currently used to diagnose approximately 90 of all individuals with type 2 diabetes. However, it is important to understand that postprandial hyperglycemia will precede fasting hypergly-cemia and should be strongly considered to screen patients, particularly those at risk.

Clinical presentation of diabetes

Biochemical investigation of patients with type 1 diabetes shows that they have absolute insulin deficiency. Hyperglycemia occurs due to a lack of the effect of insulin to inhibit production of glucose by the liver, which continues unopposed. In the absence of insulin, fat stores are broken down (lipolysis) and increased amounts of free fatty acids reach the liver. Once at the liver, the fatty acids are further metabolized into ketone bodies that circulate in the bloodstream and, once present in excess, produce an acidosis of the bloodstream. Weight loss occurs in type 1 diabetes due to a combination of breakdown of fat and lean tissue and dehydration. Uncontrolled type 1 diabetes with high blood glucose, excess ketone bodies, and acidosis (diabetic ketoacidosis) is a medical emergency requiring hospital admission. Patients with type 1 diabetes have absolute insulin deficiency and require long-term insulin therapy for continued well-being. Type 2 diabetes usually presents in adults...

Longterm complications

The possibility ofdeveloping long-term complications is one ofthe most frightening aspects of diabetes. Prolonged periods of high blood sugar increase the risk of complications in people with diabetes. Common ailments include cardiovascular disease (such as high blood pressure and atherosclerosis), eye disorders, kidney disease, nerve disorders, and foot and leg problems. Most of these conditions result from years of chronic high blood sugar levels. The good news is that many ofthe possible problems can be treated, and often the treatment is most effective when the complications are noticed at an early stage. This is why you will be asked to go for regular medical check-ups.

Longterm complications of diabetes

Diabetes mellitus is a long-term disorder associated with a number of clinical problems causing ill health and death. Disease affecting the small blood vessels in the retina, kidney, and peripheral nerves appears to be most directly related to the duration and severity of the raised blood glucose (hyperglycemia). These complications are termed microvascular and may result in blindness, chronic renal failure requiring dialysis, and nerve damage to the feet contributing to the formation of foot deformity and ulceration. Large blood vessels are also affected (macrovascular disease) in the heart, brain, and peripheral circulation. People with diabetes have higher rates of coronary heart disease,4849 stroke,50 and peripheral vascular disease51 compared to similar subjects of the same age and sex. This contributes significantly to the higher rates of ill health and early death in people with diabetes.

Poor Timing Of Fat Oxidation In Obesity Glucose Induced Fat Inhibition

More than a decade ago, the author's laboratory began to assess substrate competition in type 2 diabetes and obesity from the perspective of whether fat oxidation is appropriately regulated during fasting conditions. Using arteriovenous limb balance methods to assess oxygen and carbon dioxide exchange across the leg, we observed an elevated RQ across the leg after an overnight fast in type 2 DM (20), which denoted a decreased reliance on fat oxidation. Furthermore, there was reduced fractional extraction of fatty acids across the leg in type 2 DM (21). Experimentally, in lean, healthy volunteers, an increase in RQ across the leg was induced by hyperglycemia, even without elevation of insulin or marked suppression of plasma fatty acids an even more pronounced effect was observed in obese, nondiabetic individuals (22). Thus, increased glucose availability was associated with depressed reliance on fat oxidation during fasting conditions. The elevated RQ response was associated with...

Exercise and Appetite

In general, exercise neither stimulates nor suppresses appetite. In uncontrolled patients with diabetes or impaired glucose tolerance, by enhancing insulin activity, particularly in the postprandial period, glycemic excursions are reduced, and these excursions can play a role in stimulating appetite. For those with postprandial hyperglycemia, a brisk walk 1-2 h after eating can enhance glycemic control. In fact, exercising in a fasting state may result in increased eating after the workout, thus these individuals would be better advised to pursue the postprandial exercise approach.

How does diabetes affect your nerves

Diabetes can affect your nerves in two ways as with the eyes and kidneys, the blood supply may be affected, or there can be direct damage to the nerves as a result of high blood glucose. Any kind of nerve damage is known medically as neuropathy. The consequences will depend on which of the three types of nerve is affected.

Diabetes treatment options

Diabetes physicians have traditionally focused on treatments to reduce hyperglycemia. Good evidence from randomized, controlled trials now indicates that reducing hyperglycemia reduces the risk of microvascular complications of diabetes.4655 Subjects with diabetes also carry at least a doubling of risk of cardiovascular disease.56 Whether lowering glucose improves cardiovascular risk is currently uncertain, but the effect, if present, is likely to be modest.4656-59 Potential treatments for lowering glucose in diabetes mellitus will be considered here in a rather theoretical way because this may illuminate the mechanisms by which some of the evaluated plant treatments have an effect (Table 1.3).

Chemically Induced Diabetes Mellitus

Guinea pigs, hamsters, dogs, and monkeys. While the agents are specific for P-cells, not all animals develop the same degree of diabetes. Investigators usually test the animals for hyperglycemia prior to including each animal in a study. The animals may also develop mild damage to other organs, such as the kidneys, liver, and exocrine pancreas. Investigators have also found that there is some damage to a-cells (producing glucagon) and potentially other endocrine cells in the pancreas (6-8). In my experience, the animals often lose weight while developing diabetes. This weight loss could influence wound healing, since short-term weight loss may have significant effects on healing.

Oral Agent Classes Sulfonylureas

Sulfonylureas are indicated when hyperglycemia cannot be controlled with exercise, diet, and therapeutic lifestyle changes. They bind to a specific receptor on the pancreatic P-cells that enhances the effect on glucose lowering resulting from a closure of the potassium-dependent adenosine triphosphate (K-ATP) channel. Glimepiride (Amaryl) binds to a different protein than the other sulfonylureas, but on the same site as the potassium channel. The subsequent reduction in plasma glucose results in secondary improvement in insulin action. Some concern has been raised recently with regard to the closure of the potassium channel because this channel may play a role in cardiac tissue in coronary artery vasodilatation.

The Insulin Glucagon System Pancreas

The two first, insulin and glucagon, are essential in the normal regulation of blood glucose, which is maintained at a level of 80 mg 100 mL (or 80 V ). The third one could have an influence in the case of diseased pancreatic cells, such as tumors leading to hyperglycemia. The fourth sometimes called the hunger hormone because it might stimulate the hunger center in the hypothalamus suppresses SS secretions from gut and pancreas and pancreatic enzyme output, too. However, its function is not known yet. All four are dumped into the portal blood and pass through the liver before getting into the general circulation. The curves shown in the central part of Figure 2.69 represent blood glucose (vertical axis) with insulin and glucagon concentrations, respectively, also in blood (horizontal axis). An increase in blood insulin produces a decrease in the concentration of blood glucose (curve In) while the opposite occurs when blood glucagon goes up (straight line Gl). The crossing point, Q,...

The aGlucosidase Inhibitors

The nonsystemic a-glucosidase inhibitors are used primarily to control postprandial hyperglycemia by delaying the absorption of polysaccharides and disaccharides in the intestinal brush border. They can be used as initial agents or in combination therapy. Recent trials have indicated that patients placed on acarbose can reduce their risk of developing cardiovascular events.

Species of Plants Reported to Be Used Traditionally to Treat Diabetes

Steroidal glycosides decrease blood glucose and stimulate glycogen synthase. Promotes peripheral sensitivity to insulin rather than altering secretion of insulin (Choi and Park, 2002) Extracts lower blood glucose and increase sensitivity to insulin (Miura and Kato, 1995) Variety natalensis protects pancreatic islet -cells from toxins by acting as a radical scavenger (Beppu et al., 2003) antihyperglycemic in STZ-treated mice (Beppu et al., 1993) Maintains glucose homeostasis in Farnsworth, 1995) Used to treat diabetes (Marles and Farnsworth, 1995) Lowers blood glucose in rabbits (Garcia, 1944)

Oral Agent Combinations

Less than 20 of patients with type 2 diabetes presenting to primary care physicians offices with an initial glucose of 200-240 mg dL (hemoglobin A1-C of 9-10 ) will be able to reach a hemoglobin A1-C of less than 7 if treated with maximal doses of a sulfonylurea or metformin alone. With newer guidelines lowering the desired goal for hemoglobin A1-C to 6.5 , the majority of patients seen in primary care offices with this degree of hyperglycemia will require combination therapy to achieve the 6.5 A1-C goal. Even patients with initially good responses to a single agent will subsequently require a second or even a third agent in the future because of the progressive nature of type 2 diabetes, dietary indiscretion, and noncompliance.

Metformin and Nateglinide

Other trials have shown more robust reduction of A1-C levels by 1.4 with the nateglinide metformin combination, with fasting glucose reductions of 40 mg dL. The nateglinide metformin combination is ideal for overweight patients whose primary disturbance is postprandial hyperglycemia with A1-C less than 8 .

LDL Total cholesterol HDL [Triglycerides5

The answer is d. (Fauci, 14 e, p 1953. Tierney, 39 e, pp 1177-1182, 1193.) Diabetics with peripheral neuropathy are susceptible to developing a Charcot joint. The insensitivity of the feet predisposes the patient to multiple silent fractures causing a deformed joint. The Somogyi effect is nocturnal hypoglycemia, which stimulates a surge of counterregulatory hormones to produce a high fasting blood sugar in the morning. The Dawn phenomenon is morning hyperglycemia from reduced sensitivity to insulin in the morning hours evoked by spikes of growth hormone released during sleep. The Whipple triad is characteristic of hypoglycemia and consists of (1) hypoglycemic symptoms, (2) low fasting blood glucose, and (3) immediate recovery after administration of glucose. The Whipple triad is seen in any disorder that causes hypoglycemia (not only with insulinoma). Mature-onset diabetes of the young (MODY) is a rare autosomal dominant disorder characterized by impaired insulin secretion and...

ASomatotropic Hormone Growth Hormone

(1) The target organs of this hormone are the growing structures of the body. This hormone influences such structures to grow. Growth is produced because cell division is increased--stimulating increased growth of all tissues capable of growing. This hormone produces an increased utilization of amino acids to produce proteins. It also causes a renal depression followed by accumulation of sodium chloride and water. Inhibition of carbohydrate utilization also occurs, producing hyperglycemia.

Shortacting Insulins And Their Analogs

Duration of action (4-5 hours) than human regular insulin (6-10 hours) when given subcutaneously, causing less hypoglycemia and better postprandial glucose control with lower postprandial glycemic excursions. These analog insulins are ideal add-ons for regimens that include long-acting and intermediate-acting insulins or for patients maximized on oral therapy who need coverage for intermediate postprandial hyperglycemia caused by stress, variations in diet, or medication adjustments (23). Postprandial hyperglycemia can be addressed when and if it occurs, reducing the likelihood of glucose toxicity and providing the patient with a go to regimen when postprandial excursions occur (the postemptive approach). A convenient regimen is to give 2 U of a short-acting analog insulin for every 50 mg dL elevation in postprandial glucose. This scale for postprandial glucoses is as follows

Items 738 through 741

A 26-year-old gravida 3 woman has a history of gestational diabetes and a delivery of two previous infants at term that were greater than 4000 g, each of whom had severe hypoglycemia. Which of the following maneuvers is least likely to reduce the chance of the next child's having hyperglycemia

Phillippa Miranda and Diana McNeill

Case a 51-year-old woman who has had type 2 diabetes for five years is managed with metformin, diet, and exercise. She notes worsening hyperglycemia, but attention to diet and exercise does not seem to improve glycemic control as it has in the past. She mentions to her physician that she has missed her last two menstrual periods and that she seems to be a bit more edgy. She wonders whether there is a correlation between her worsening diabetes control and her menstrual changes.

Screening of asymptomatic individuals

Since hyperglycemia can be asymptomatic, those individuals at increased risk for diabetes should be screened at regular intervals. Individuals at increased risk for type 2 diabetes include those with increasing age, obesity, and lack of physical activity. Obesity is a major contributing factor to insulin resistance and diminished beta-cell reserve capacity in type 2 diabetes even those patients who are not overweight by standard criteria may have an increased percentage of body fat and or an abnormal distribution predominantly in the abdominal

Nuts Seeds And Oils

The polyphenolics in olive oil inhibit LDL oxidation by scavenging free radicals and chelating free metal ions.149 The polyphenolics also enhance the synthesis of prostacyclin, PGI2, and thus inhibit platelet aggregation. These phenolic compounds are antioxidants that reduce eicosanoid production by leukocytes, so as to modulate inflammation and protect the cell against cancer-forming substances. Olive oil also contains up to 150 ppm of the antioxidant vitamin E, which can also inhibit platelet aggregation. Polyphenolics have also been shown to lower blood glucose levels.151

Proposed Physiological Mechanisms

Meals that are high in GI challenge these regulatory mechanisms, as presented in Fig. 1. To illustrate the dynamic changes that occur following a meal, the postprandial period can be divided into early, middle, and late phases (60). During the early phase (0-2 h after a meal), hyperglycemia can be more than twofold greater following consumption of a high-GI food (e.g., potatoes) compared with a macronutrient-controlled portion of a low-GI food (e.g., legumes) (24,61). Exaggerated hyperglycemia accentuates release of gut hormones and promotes primary hyperinsulinemia, along with hypoglucagonemia. This hormonal milieu enhances the normal anabolic response to feeding described above. The middle postprandial phase (2-4 h after a meal) is marked by a decline in nutrient absorption from the gastrointestinal tract. However, persistent elevation of circulating insulin relative to glucagon stimulates continued glucose uptake by insulin-sensitive tissues, often causing a rapid drop in blood...

Type 2 Transglutaminase and Cell Death

Although it is now clear that TG2 biochemistry has multiple and unique cellular features, knockout (KO) mice carrying the homozygous deletion of TG2 gene on a mixed background do not exhibit an embryonic lethal phenotype they are viable and born with Mendelian frequency 31, 32 . Under normal physiological conditions TG2 KO animals do not show major anomalities 31-32 . Moreover, no obvious alterations have been observed in the onset of apoptosis, in the ECM structure or in the heart function, in which TG2 G-protein activity is thought to be important 31, 32 . However, when cell death is induced in vivo in KO mice, the clearance of apoptotic cells by phagocytosis is defective in the thymus and in the liver and inflammatory as well as autoimmune reactions develop in the animals 33 . The most obvious explanation for the lack of lethal phenotypes is that other transglutaminases may exert a compensatory effect in mammalian tissues. However, such compensation is necessarily partial, since...

Diseasespecific Guidelines

The physiological advantage of an emphasis on plant foods may also stem from the influence of these foods on blood sugar control, where there is renewed interest in the role of foods with a lower glycemic index. Whole foods and foods rich in unrefined starch and fiber produce a more blunted postprandial blood sugar response and effectively control hunger than those based on highly refined carbohydrate foods.

General Health Status

Basic laboratory investigations to be performed on all patients considered for AAA surgery include a full blood count, erythrocyte sedimentation rate (ESR), blood glucose, serum urea, and electrolytes. Hematological disorders and anemia may well be uncovered at this stage, prompting further investigation before surgery. An elevated ESR might be the only indicator of an inflammatory AAA or even reflect ongoing chronic infection or inflammation elsewhere. Hyperglycemia may expose the unknown diabetic and has implications for both peri- and postoperative patient care. Silent renal or endocrine dysfunction is suggested with abnormal urea and electrolyte values, and these would necessitate further investigation and optimization before surgery.

Expression Of Ectopic Proteins In Pomc Cells

The identification of promoter elements sufficient for directing cell-specific gene expression has great value for the design of cell biological and physiological experiments in vivo. Targeting of SV40-Tag and HSV1-TK discussed here are two examples. POMC-promoter transgenics have also been used in several other systems. A particularly intriguing use has been the ectopic expression of proinsulin in transgenic intermediate-lobe melanotrophs (70,71). Because of their complement ofprohormone convertases, the proinsulin is efficiently processed to mature, biologically active insulin. Transplanted intermediate-lobe tissue from these transgenic mice into syngeneic diabetic nucleotide-binding oligomerization (NOD) mice effectively reversed the hyperglycemia and diabetic symptoms. Allografts ofthe islet tissue showed extensive neovascularization and enhanced viability compared to transplanted pancreatic islets. The favorable autoimmune profile of melanotroph cells compared to pancreatic...

Agouti and Agouti Related Protein AGRP

Normal (wild-type) alleles at the agouti locus in the mouse act on the hair follicle and control deposition of pigment in the emerging hair. Deposition of yellow pigment near the tips of the hair, followed by deposition of black pigment in the remainder of the hair, produces a characteristic uneven brownish coloration of the animal, referred to as agouti (named after a similarly colored South American rodent). Two dominant mutations at the agouti locus, yellow (or lethal yellow, Ay) and viable yellow (Avy) produce increased growth, obesity, hyperinsulinemia, and hyperglycemia in combination with altered fur color bright yellow in Ay and various degrees of yellowing in Avy. These striking phenotypic alterations are believed to be mediated by ectopic expression of the agouti protein, because ubiquitous expression of either agouti protein or closely related AGRP in transgenic mice produced a phenotype closely resembling the abnormalities of the yellow (Ay) mouse (125,152). A similar...

Irregularities Of Insulin Therapy

Hypoglycemia and hyperglycemia are two of these potential difficulties. b. Hyperglycemia (Diabetic Coma). Hyperglycemia (diabetic coma or acidosis) results from the patient's neglecting to maintain proper dieting habits, the patient's missing of required insulin doses, the patient's taking an underdose of insulin, or from the patient's taking the insulin in doses that are too far apart. Hyperglycemia can be treated with the administration of insulin. It is best that the patient's physician be made aware of the patient's condition as soon as possible. This is necessary because the patient's dosage of insulin might have to be changed.

Species of Plants Reported to Be Used Traditionally to Treat

Extracts decrease blood glucose (Gallagher et al., 2003) Ethanol extracts increase insulin release from INS-1 cells (Hussain et al., 2004) Ethanol extracts inhibit carbohydrate-hydrolysing enzymes (Kim et al., 2004) Used to treat diabetes (Marles and Farnsworth, 1995) Used to treat diabetes (Lewis, 1977)

The answer is d Fauci 14e pp 21162118 Gynecomastia is

The answer is a. (Tierney, 39 e, pp 1152-1157.) Hyperosmolar hyperglycemic nonketotic state (HHNKS) is seen in patients with NIDDM and is usually precipitated by an illness. The patient's residual insulin prevents lipolysis and ketogenesis. Diabetic ketoacidosis (DKA) is due to an absolute deficiency of insulin relative to the counter-regulatory hormones. The result is gluconeogenesis, ketogenesis, lipolysis, and decreased glucose uptake causing hyperglycemia and a metabolic acidosis. Kussmaul respiration is a respiration pattern of increased tidal volume seen in patients with metabolic acidosis (i.e., DKA). Gestational diabetes occurs in 3 of pregnancies all women should be screened between the 24th and 28th wk of pregnancy. Complications of undiagnosed gestational diabetes include macrosomia and neonatal hypoglycemia. Impaired glucose tolerance is defined as a 2-h plasma glucose of 140-200 mg dL after a glucose load of 75 g in a patient whose fasting blood glucose is normal.

Congenital Adrenal Hyperplasia

Labs CBC leukocytosis (14,000) (without infection). Lytes hyponatremia (130 mEq L). ABGs markedly reduced bicarbonate (10 mEq L) acidosis (pH 7.1). Increased ketones in blood increased creatinine hyperglycemia increased anion gap (between 10 and 18) (anion gap is calculated as follows Na + K - C1 + HC03 ) increased amylase (without pancreatitis). UA glycosuria ketonuria.

The Effect Of A Vegetarian Diet On Performance

Nineteen long-term (mean of 46 years) vegetarian and 12 non-vegetarian, healthy, physically active elderly women (mean age of 71 years) were compared on a variety of hematological, anthropometric, and metabolic factors.30 Although the vegetarian subjects had significantly lower blood glucose and cholesterol levels, no differences between groups were found for submaximal and maximal cardiorespiratory and electrocardio-graphic parameters measured during graded treadmill testing. The authors

Insulinomimetic Agents

Fasting hyperglycemia in type 2 diabetes is mainly determined by unrestrained hepatic glucose output (HGO) thus, any treatments that reduce HGO will lower glucose levels. This is one major mechanism whereby metformin seems to have its antidiabetic activity, although the molecular pharmacological mechanism by which it is achieved is debated. One of the main actions of insulin in lowering blood glucose concentrations is by a reduction in HGO. Because one of the main effects of glucagon is to increase HGO, any method to impair glucagon's action will also tend to reduce blood glucose.6 The antidiabetic activity of GLP-1 in type 2 diabetes has been partially attributed to lowering of glucagon concentrations65 and glucagon receptor antagonists are in development.6 Alternatively, inhibiting the hepatic enzymes involved in glycogenolysis or hepatic gluconeogenesis would be expected to reduce HGO.72 Loss of glucose in the urine (glycosuria) usually occurs at a variable threshold when arterial...

How does diabetes affect your kidneys

One-third of people with type 1 diabetes and 10-20 per cent of people with type 2 diabetes develop kidney disease after living with diabetes for 15 years or more. To understand how this complication develops, you need to know a little bit about the structure and function of the kidneys. The kidneys maintain the body's internal environment by controlling its fluid and electrolyte levels, and by removing its waste products. Each kidney contains approximately one million microscopic units called nephrons, which filter out waste products from the blood. Over long periods of time, high blood sugar levels damage the tiny blood vessels in the kidneys, making them thicker and clogged, and impairing the filtering ability of the nephrons. As a result, they are less able to filter wastes and impurities from the blood properly. Waste products in the bloodstream then build up to harmful levels. At the same time, some of the nutrients and proteins that should remain in the blood leak out of the...

Genetic or Spontaneous Diabetes Mellitus Models

The discovery and development of the obese mouse strains is an interesting story of scientific discovery. Dr. Coleman, at Jackson Laboratories (Bar Harbor, ME), noticed that some C57BL mice developed obesity and profound hyperglycemia. The obesity was found to be the result of an insatiable hunger. The animals literally ate continuously, gaining two to three times the weight of littermates. In addition to obesity, the animals developed insulin-resistant diabetes. Breeding studies demonstrated that the animals were sterile, but that normal littermates carried the gene (28). Coleman and Hummel (29) did parabiosis studies, in which obese animals were connected to normal animals through their blood supply. In one strain, the ob ob mouse, the obese mouse would lose weight to match the normal attached animal. Coleman surmised that a satiety hormone was missing from the mutated ob ob mouse. In another strain, the db db mouse, the attached normal animal essentially starved itself to death,...

Classification of diabetes

Diabetes mellitus is not a single disorder, but a collection of conditions with a common end result of raised blood glucose. Two main types of diabetes account for more than 95 of all cases of diabetes a minority of cases are due to various specific metabolic or genetic causes. Type 1 diabetes is a condition due to absolute insulin deficiency secondary to autoimmune destruction of the insulin-containing P-cells of the pancreas gland. Type 2 diabetes is a condition due to relative insulin deficiency and or impaired biological response to insulin (insulin resistance).15 Type 1 diabetes probably represents 5 to 10 of all cases of diabetes, and type 2 diabetes accounts for 85 of all cases. Other forms of diabetes may be secondary to other metabolic disorders, such as the endocrine disorder acromegaly in which excessive production of growth hormone inhibits the action of insulin or due to pancreatic problems (e.g., after surgical removal of pancreas) (Table 1.1). Individuals are usually...

The Natural History Of Type 2 Diabetes

Although both insulin resistance and impaired insulin secretion precede the development of postprandial hyperglycemia and the subsequent type 2 diabetic phenotype, insulin resistance is more prominent in the prediabetic state and plays an important role in the pathogenesis of macrovascular disease. Insulin resistance is commonly the earliest manifestation in the development of type 2 diabetes, typically originating 5-10 years before postprandial glucose levels in the diabetic range (200 mg dL). As long as the P cell is able to compensate by increased insulin production, normal glucose tolerance is maintained. Thus, not all patients with insulin resistance will develop diabetes (8). Insulin resistance can be worsened by genetic factors, elevated free fatty acids, hyperglycemia, pregnancy, obesity, sedentary lifestyle, aging, and various medications (i.e., steroids, cw-retinoic acid, estrogens, nicotinic acid, oral contraceptives, phenothiazines, and antipsychotic agents). Insulin...

Trophic Factors for Gonadotropes and Thyrotropes

TRH is expressed in the hypothalamus as well as a number of other organs. The tripeptide was originally characterized for its ability to regulate serum levels of TSH, but it also appears to function as a neurotransmitter or neuromodulator. Although TRH is a well-known regulator of TSH synthesis and secretion, its role in regulating thyrotrope development was unknown. To assess the thyrotrope-specific effects as well as any other biological target of TRH, the gene was specifically disrupted in mice. Mice lacking the TRH gene exhibit hyperglycemia, because of a profound decrease in insulin secretion, and tertiary hypothyroidism (105). Unexpectedly, although TRH levels were non-detectable in these mice, serum levels of TSH were nearly twice that of a wild-type mouse (105). This suggests that negative feedback by thyroid hormones plays a more significant role than TRH in regulating TSH levels. In other words, the loss of negative regulation by thyroid hormones was sufficient to overcome...

Introduction To Adipose Tissue

Before describing the specific actions of adipokines, it is important to understand that adipocytes have an active role in modulating normal health. Our understanding of the role of adipocytes in maintaining normal metabolism was enhanced by a series of elegant experiments that utilized mice that were genetically engineered to not express adipocytes. These fatless, or lipoatrophic, mice were found to have elevated circulating levels of fatty acids, hyperglycemia, and hypertriglyceridemia. Additional abnormalites included increased hyperglycemia and insulin resistance (2). Remarkably, transplantation of adipocytes back into the lipoatrophic mice normalized many of these metabolic parameters. These observations could be explained by the fact that adipocytes serve as a reservoir of fatty acids and or secrete hormones that modulate systemic metabolism.

What goes wrong

Insulin has a unique shape that plugs into special sockets or receptors on the surface of cells throughout the body, and by plugging into these receptors, insulin not only makes cells extract glucose from the blood but also prevents them from breaking down proteins and fat. It is the only hormone that can reduce blood glucose, and it does this in several ways Other mechanisms in the body work in conjunction with insulin to help to maintain the correct level of blood glucose. However, insulin is the only means available to the body of actually lowering blood glucose levels, and when the insulin supply fails, the whole system goes out of balance. After a meal, there is no brake on the glucose absorbed from what you have eaten, so the level of sugar in your blood continues to rise. When the concentration rises above a certain level, the glucose starts to spill out of the bloodstream into the urine. Infections such as cystitis and thrush can develop more easily when the urine is sweet as...

Insulin

Insulin, a hormone secreted by pancreatic beta cells, regulates metabolism of carbohydrates and is responsible for maintaining a constant blood glucose level. Insulin lowers blood glucose levels by promoting the transport of glucose from the bloodstream into the cells. Insulin levels can be measured by radioimmunoassay, a technique that uses radioactive substances to determine the concentration of specific blood constituents. Insulin levels are reported as microunits per milliliter ( xU mL).

The Pancreas

The other accessory organ important to the gastrointestinal tract is the pancreas. The pancreas functions as both an endocrine and exocrine gland and it is the exocrine portion that is concerned with digestion. The pancreas secretes lipases and proteases that are responsible for the digestion of fats and proteins in the small intestine. The endocrine portion of the pancreas is composed of groups of cells scattered throughout the pancreas called the Islets of Langerhans. There are alpha and beta cells in the pancreas. These alpha and beta cells have specific functions. The alpha cells secrete glucagon, a hormone which promotes the breakdown of glycogen and sugar stores and causes their release into the bloodstream. The beta cells secrete insulin, a hormone which promotes the movement of glucose from the bloodstream into the cells and the subsequent oxidation of the glucose. The release of insulin promotes a lowering of blood sugar. Diabetics have insulin deficiency and hence have...

What is diabetes

Diabetes mellitus is a metabolic disorder characterized by a predisposition to developing significantly raised blood glucose. The first recorded description of diabetes mellitus dates back to the Ebers papyrus in Egypt around 1500 b.c.1 Diabetes mellitus has been noted in almost all ancient cultures with a tradition of written language such as Vedic, Chinese, Arabic, and Mediterranean Symptoms of diabetes mellitus include increased thirst as well as increased frequency and volume of urine production. These classical symptoms led to its naming from the Greek word for a passing through, SiaPn n0 (Sia through or by Paivro a passing). Diabetes mellitus may lead to death if left untreated due to acute metabolic decompensation producing dehydration and acidosis. Even with treatment, over a period of years, elevated blood glucose levels result in damage to a number of organs, including the eyes, kidneys, nervous system, and blood vessels. Insulin is the major regulator of blood glucose...

Gestational Diabetes

Gestational diabetes most often develops between the 24th and 28th week of pregnancy, occurs in 2-5 of pregnancies, and usually disappears after birth. Gestational diabetes is more common in older, obese, or diabetes-prone ethnic groups, and in those with a positive family history. Most (80-94 ) women with gestational diabetes will return to normal after delivery. Hispanic females and Native Americans are especially prone to developing diabetes after an episode of gestational hyperglycemia, with the occurrence rate being as high as 50 within 5 years of pregnancy termination. The other gestational diabetics will have a 30-40 chance of developing diabetes in 10-20 years.

Hypothermia

Include acute and subacute hemorrhage and dehydration fluid loss into an extravascular compartment can significantly reduce intravascular volume and result in nonhemorrhagic hypovolemic shock. Acute pancreatitis, loss of the enteral integument (from conditions such as burns and surgical wounds), or occlusive or dynamic ileus can all induce oligemic hypotension as a result of extravasation of fluids into the extracellular compartment. Other forms of water and solute loss, such as diarrhea, hyperglycemia (leading to glucosuria), diabetes insipidus, salt-wasting nephritis, protractcd vomiting, adrenocortical failure, acute peritonitis, and overzealous use of diuretics, can also lead to decreased intravascular volume and hypovolemic shock.

Retinopathy

In the milder form, known as nonproliferative retinopathy, high blood sugar levels damage the delicate blood vessels that nourish the retina. This may cause the blood vessels to become weak or close off, and leak blood, fluid, or fat into the fluid surrounding the retina. If the leakage affects the macula (the part ofthe eye where vision is sharpest), then the result is blurred vision.

Atherosclerosis

People with diabetes have an increased risk of developing atherosclerosis, because of the interaction of a number of factors but most importantly because high blood glucose affects the tissue that lines the inner surfaces of the coronary arteries. This causes the release of harmful chemicals that create a sticky surface and makes the inner walls of the arteries more susceptible to plaque formation. When atherosclerosis develops, it affects not only the coronary arteries but also all the other arteries. When the arteries in the brain become seriously narrowed, the result is a stroke. The vast majority of strokes occur because of arterial blockage. In the legs, serious atherosclerosis is known as peripheral vascular disease. Peripheral vascular disease is an underlying factor in the development of many of the lower

Summary

Fasting (premeal) hyperglycemia is caused by increased hepatic glucose production, decreased basal insulin secretion, reduced insulin sensitivity, and high sustained postprandial glucose levels. For individuals with AM fasting hyperglycemia, be aware of suppertime postprandial excursions and bedtime snacks. All oral agents are effective in 2. Levels of postprandial glucose are regulated by preprandial glucose levels, insulin sensitivity, and bolus or first-phase insulin release. Oral agents effective in reducing postprandial hyperglycemia include the glinides (repaglinide and nateglinide), a-glucosidase inhibitors, and, to a lesser extent, the TZDs and biguanides.

Mixed Insulins

Continued subcutaneous infusion still supplies state-of-the-art, and the best, coverage, because insulin pumps can deliver short-acting insulin continuously and specifically according to glucose patterns. The ability to supply a bolus insulin injection at the touch of a button according to elevated blood glucose results are caused by varied carbohydrate and caloric intake, physical activity, and other factors, provides an added benefit to continued subcutaneous infusion of insulin (22).

Premixed Insulins

One of the criticisms of fixed-dose combinations is that inconsistent blood glucose readings increase the risk of hypoglycemia and hyperglycemia compared with regimens that segregate and vary the intermediate-acting and short-acting insulin doses based on dietary needs and irregularities. The fixed-dose combinations are not as easy to titrate as doses of only the shorter-acting analog insulins adjusted according to daily needs.

Novel Therapeutics

An exciting area of diabetic therapeutic vistas is amylin. This hormone is also released from the P-cells of the pancreas. Amylin, however, suppresses glucagon, which is produced in the a-cells of the pancreas, and enhances hepatic gluconeogenesis. In nondia-betic patients, the a-cells secrete more glucagon when blood glucose levels fall and less glucagon when glucose levels are high. In diabetic patients, however, glucagon levels may remain high despite high blood-glucose levels. This may contribute to high postprandial sugar levels. Another interesting aspect of amylin's physiological effects is its neuroendocrine mode of action. Bilateral vagotomies have been shown to abolish the effects of amylin. Amylin has been shown to be efficacious in decreasing gastric emptying, but this effect seems to be dependent on serum glucose levels. Thus, in situations associated with hyperglycemia, amylin slows gastric emptying, whereas this effect is minimized in hypoglycemic states. receiving the...

Definitions

Diabetes mellitus refers to a group of common metabolic disorders characterized by hyperglycemia. Diabetes may be type 1 (juvenile-onset or insulin-dependent diabetes mellitus - IDDM), type 2 (adult-onset or non-insulin-dependent diabetes mellitus - NIDDM), or gestational (during pregnancy). In type 1 diabetes, hyperglycemia is caused by an absolute deficiency of insulin secretion. In type 2 diabetes, hyperglycemia is caused by a combination of insulin resistance and inadequate compensatory insulin secretory response, with a relative, not absolute, insulin deficiency.

Legumes

A number of studies have shown that legumes, such as beans and lentils, lower blood cholesterol levels, improve blood sugar control, lower triglyceride levels, and lower the risk of heart disease.74-76 While beans are good sources of polyunsaturated fat, folic acid, potassium, copper, and soluble fiber, they also contain a variety of important phytochemicals such as flavonoids, protease inhibitors, saponins, phytates, and phytosterols that have cardio-protective and cancer-preventive properties.3,77,78 The anthocyanin pigments isolated from the bean seed coat of Phaseolus vulgarus, the common bean, exhibit strong antioxidative activity.79 These pigments may provide protection against oxidative damage of cell membrane lipids and cell contents.

Signs and symptoms

In mid life, type 2 diabetes is the most common type of diabetes. The diagnosis of type 2 diabetes is based on symptoms of hyperglycemia and the measurement of elevated blood-glucose readings. The classic symptoms of significant hyperglycemia include polyuria, polydipsia, weight loss, polyphagia, and blurred vision. Hyperglycemia may also cause fatigue, vaginitis, or other non-specific symptoms, which maybe attributed to menopause. If the onset of hyperglycemia is gradual, then there may not be any symptoms, thus delaying the diagnosis of diabetes.

Diagnostic criteria

Diagnostic criteria and classification schemes for diabetes have been proposed and published by the ADA and the WHO.5'6 In January 2002, the ADA published revised criteria for the diagnosis of diabetes, which state that diabetes can be diagnosed by any one of three criteria (Table 15.3). In the absence of unequivocal hyperglycemia with metabolic decompensation, the criteria should be confirmed by repeat testing on a different day. The OGTT is not recommended for routine clinical use, but it maybe necessary when diabetes is suspected despite normal fasting plasma glucose.5 The ADA does not recommend glycosylated hemoglobin (hemoglobin A1c, HbAlc) for the diagnosis of diabetes. Even though HbAlc is a reliable marker of glycemia over a period of about two to three months, this test should not be used to diagnose diabetes because too many different methods are used for the measurement of HbAlc, and the correlations between fasting plasma glucose, two-hour post-load glucose, and HbAlc are...

Case

The patient has been continuously frustrated with failure to achieve desired hemoglobin A1-C and by fluctuating blood sugars with symptomatic episodes of both hyperglycemia and hypoglycemia. This case illustrates a failure on the mixed insulins. This patient would do extremely well with bedtime glargine administration. Many patients faced with this dilemma achieve better hemoglobin A1-C results and feel better as result of less glycemic excursions when glargine is used. These patients usually have less hyperglycemia by using the basal insulin glargine and have a better quality of life with better self-esteem as a result of enhanced glycemic control and attenuation of postprandial excursions.

Medical 169

The woman is having an exercise-induced hypoglycemic episode. Exercise stimulates the uptake of glucose from the blood, thus lowering blood glucose levels. The normal response to this is to decrease blood insulin levels and increase glucagon levels, thereby stimulating glycogenolysis and restoring blood glucose. However, this person has type 1 diabetes mellitus and her insulin levels are determined largely by injection. Therefore, the insulin glucagon ratio remained high, glycogenolysis could not be stimulated, and hypoglycemia resulted. It is time for her to ingest glucose in some readily absorbed form that should be carried by all type 1 diabetics.

Diabetes Mellitus Dm

An 8-year-old boy is seen in the emergency department with vomiting and abdominal pain of 2 days' duration. His mother states he has been drinking a lot of fluids for the past month, and reports weight loss during that time. Physical examination reveals a low-grade fever, and a moderately dehydrated boy who appears acutely ill. He is somnolent but asks for water. Respirations are rapid and deep. Laboratory tests reveal a metabolic acidosis and hyperglycemia. Diagnostic Tests. Diabetic ketoacidosis (DKA) occurs when the glucose is > 300 mg dl and there is ketonemia, acidosis (pH < 7.30 bicarbonate, 15 mEq L), glucosuria, and ketonuria. DM can also be diagnosed in patients with milder symptoms. The new criteria are symptoms of diabetes with a random plasma glucose > 200 mg dl, or fasting glucose > 126 mg dl, or 2-h glucose tolerance > 200 mg dl. In all cases, hyperglycemia and glucosuria are necessary.

Clinical Trials

Among all of the lipid-lowering agents, nicotinic acid can favorably modify all of the lipoprotein abnormalities associated with atherogenic dyslipidemia according to the National Cholesterol Education Program III report. The problem with niacin has been its side-effect profile (flushing, hepatotoxicity, hyperglycemia, and gout), reduced potency for LDL reduction and reduced outcomes data compared with the statins (26).

Diabetes

Poor blood sugar control will impair the patient's recovery by promoting infection, and slow wound healing. Most hospitals will have a set guideline devised by the diabetologists to ensure that diabetic surgical patients are cared for appropriately. These will usually involve a post-operative infusion of insulin according to a sliding scale, and an infusion of a set concentration of dextrose, which will be discontinued when the patient is able to return to their normal diabetic regimen. It is important that the patient receives both infusions together if dextrose only is administered, hyperglycaemia can result whereas the administration of insulin only will result in hypoglycaemia. These infusions are usually given through a dedicated cannula via infusion pumps, and it is essential that the function and patency of these is checked at regular intervals. Tight blood sugar control has been shown to improve the survival of patients after heart attacks, and those who are critically ill.

Brown Adipose Tissue

To test this hypothesis, several lines of transgenic mice with selective ablation of the brown adipose tissue have been generated. In these mice, the regulatory elements of the brown adipose tissue-specific UCP protein gene were used to drive expression of DTA transgene resulting in specific ablation of brown adipose tissue. These mutants are characterized by reduced energy expenditure (lower body temperature but not locomotor activity), marked obesity, increased food intake, hyperglycemia, hyperlipidemia, and increased susceptibility to a high-fat diet induced obesity (151,158-160). These abnormalities are associated with insulin resistance and non-insulin-dependent diabetes mel-litus (NIDDM) with both receptor and postreceptor components (161,162). Interestingly, in this model, increased body wt, hyperlipidemia, late hyperphagia, and glucose homeo-stasis are leptin-resistant, while hypothalamic NPY and the hypothalamic-pituitary-adrenal axis remain under leptin control (151,163).

Diabetes Mellitus

Diabetes mellitus is a disorder characterized by hyperglycemia (high levels of glucose In the blood) and glycosuria (glucose in the urine) resulting from inadequate production or use of insulin. (4) Hyperglycemia. Hyperglycemia refers to higher than normal levels of glucose in the blood. The normal level of glucose in the blood is 60 to 100 milligrams per 100 milliliters. Of course, the level of glucose will increase after the ingestion of food.

Types Of Insulin

Insulin Injection (Regular Insulin, Crystalline Zinc Insulin). Insulin injections may be given subcutaneously in the treatment of diabetic hyperglycemia and intravenously in the treatment of diabetic ketoacidosis. This product is available in the 40 and 100 unit strengths in a mixture of beef and pork insulin. The 100 unit strength is available as either beef or pork source. The onset of action of this product is from 30 minutes to one hour. The time required to reach the peak effect is from two to four hours. The duration of action of this product ranges from five to seven hours.

The Meglitinides

The meglitinides are more properly referred to as the glinides because repaglinide and nateglinide are not members of the same chemical class. Repaglinide is a benzoic acid derivative and nateglinide is a phenylalanine derivative. The glinides specifically target postprandial hyperglycemia, and, compared with sulfonylureas, have less risk of hypoglycemia and less continuous stimulation of the P-cells. The glinides are designed to return insulin levels to baseline between meals and to stimulate insulin secretion when needed at mealtime. The glinides, in general, are rapidly absorbed and quickly eliminated and are ideally positioned for patients with primarily postprandial hyperglycemia and modest elevations of hemoglobin A1-C (< 8 ). The glinides are ideally suited for early-stage patients with diabetes (where the predominant and, occasionally, the only abnormality is postprandial hyperglycemia), the elderly, and in patients with mild elevations of hemoglobin A1-C who have irregular...

Review Questions

As part of a study to quantify contributors of stress to hyperglycemia and ketosis in diabetes, normal hepatocytes and adipocytes in tissue culture were treated with Cortisol and analyzed by Northern blotting using a gene-specific probe. The results of one experiment are shown below. C. Hyperglycemia

Where do we go next

Other studies suggest that berberine may mediate antihyperglycemic effects by inhibiting a-glucosidase and decreasing glucose transport through the intestinal epithelium (Pan et al., 2003). Some in vitro investigations suggest that berberine exerts a glucose-lowering effect in hepatocytes that is insulin independent and similar to the action of metformin, but has no effect on insulin secretion (Yin et al., 2002). Other alkaloids with potential use in the treatment of diabetes from this group of plants include dehydrocorydaline from Corydalis turtschaninovii (Papaveraceae) tuber (Kubo et al., 1994) and tetrandrine from Stephania tetrandra (Menispermaceae) root (Liang et al., 2002 Lieberman et al., 1992). Polysaccharides from this group of plants also justify further study including aconitans A, B, C, and D from the roots of Aconitum carmichaelii (Ranunculaceae), which lower blood glucose in normal and diabetic mice (Konno et al., 1985c). Another study identified oleanolic acid as an...

Clinical Picture

Invasive fungal dermatitis has been described recently in premature newborns (< 24 weeks) after vaginal delivery and postnatal treatment with glucocorticoids (81 ) who develop of hyperglycemia (Pediatrics 1995 95(5) 682-686). It is signalled around the ninth day by the appearance of erosive and scaly lesions which provide an access for Candida causing a systemic infection (69 ).

Endocrine System

438, A 60-year-old male develops elevation of blood pressure, hyperglycemia, decreased bone density and occult blood in his stool. Which of the following agents is associated with these adverse effects 445. Which of the following drugs is least likely to cause hyperglycemia and hypokalemia

Diabetic Nephropathy

Uncontrolled hyperglycemia, hypertension, and dyslipidemia can accelerate the progression to end-stage renal disease. Microalbuminuria is indicative of abnormal vascular responses and increased permeability of the endothelium at the glomerular level. Renal cells in Bowman's capsule are particularly vulnerable to the vascular permeability of increased blood pressure that is characteristic of diabetes. Once glomerular pressure begins to increase incipiently, the glomerular filtration rate begins to drop, causing glom-erulosclerosis and subsequent progression from microalbuminuria to severe proteinuria. Hyperglycemia is a significant risk factor for diabetic nephropathy. Mean levels of hemoglobin A1-C correlate with subsequent loss of renal function. The UKPDS trial (57) showed that intensive glycemic control reduced the risk of diabetic nephropathy and other microvascular complications. The Kumomoto Study (58) in Japan showed that intensive treatment with three or more insulin...

Longacting Insulins

When combined with short-acting insulins to cover postprandial hyperglycemia, the ideal basal bolus therapeutic concept can be achieved. A large, randomized, controlled clinical study compared a basal-bolus regimen of glargine once daily at bedtime vs Humulin NPH insulin administered once or twice daily along with regular human insulin before meals as needed in both groups. Glargine had similar effectiveness as NPH (which was given once or twice daily) in reducing A1-C and fasting glucose, and showed less hypoglycemia.

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