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Objective: Idiopathic reactive hypoglycemia is defined as early postprandial hypoglycemia occurring on ingestion of high carbohydrate containing meal. Remission ensues with high protein low carbohydrate diet. This study assessed roles of insulin and glucagon in its onset and remission. Methods: Plasma glucose, insulin and glucagon were determined after an overnight fast and repeatedly until 180 minutes on ingestion of 3 meals; 100 g glucose; 100 g pure protein liquid and mixture of 50 g each at 14 days’ interval. Five adults with IRH and 6 age matched healthy volunteers participated. Results: In IRH, glucose ingestion induced prompt rise in glucose (5.1 ± 0.8 to10.5 ± 1.2 mM/L) followed later by hypoglycemia (2.6 ± 0.4 mM/L). Insulin rose from 7 ± 2 to 90 ± 18 mU/L. Glucagon rose initially (10% ± 2%) from elevated basal concentration (373 ± 57 mU/L) followed by later decline (-43% ± 12%). On protein ingestion, glucose declined followed by a restoration to basal level while both insulin and glucagon rose (28 ± 6 mU/L; 148% ± 38%, p < 0.01). However, insulin response was lower and glucagon rise was greater when compared to responses on glucose ingestion (p < 0.01). With mixed meal, glucose (8.2 ± 0.6 mM/L), insulin (65 ± 12 mU/L) and glucagon (48% ± 7%) responses were lesser than rises following glucose ingestion (p < 0.05) and hypoglycemia did not occur. Conclusion: In IRH, initial hyperglycemia on glucose ingestion may be exacerbated by paradoxical glucagon rise and hypoglycemia may be induced by increased insulin and declining glucagon responses. Resolution of hypoglycemia with high protein low carbohydrate diet may be attributed to blunting of insulin response and concurrent glucagon rise.

Background: UKPDS suggested relentless deterioration of β cell function as a part of natural course of type 2 diabetes mellitus. However, the course was apparently not universal since many patients maintained glycemic goal (HbA1c 7.0% with any therapy or HbA1c < 7.0% with insulin, either monotherapy or in combination with oral agents. β cell function is deemed “preserved” (β + ve) with HbA1c < 7.0% with treatment consisting of life style program or/and oral drugs. Results: Prevalence of b cell failure progressively rose with increasing number of microvascular complications from 0 to 2 with no further significant rise with 3 complications whereas subjects with preserved β cell function declined with increasing number of microvascular complications (p < 0.01 for both groups). Significant relationships were also noted between the age and the duration of diabetes and prevalence of β cell failure (p < 0.01). The relative risks rose progressively for β cell failure/β cell preserved with increasing number of microvascular complications as well as the greater duration of Diabetes. However, a significantly (p < 0.01) higher relative risk for β cell failure persisted for rising number of microvascular complications even after eliminating the influence of age and duration of diabetes. Conclusion: β cell failure may be a manifestation of microvascular pancreatic isletopathy similar to other microvascular complications.

Background: Lack of first phase insulin secretion during oral glucose tolerance test [OGTT] in Type 2 Diabetes Mellitus (DM) is attributed to glucose toxicity. Alternatively, the role of insulin resistance in impaired insulin release secondary to lack of glucose entry into β cells may be responsible, but is not examined. Aim: The role of insulin sensitivity in 1st phase insulin secretion was assessed. Material and Methods: Plasma glucose (G) and insulin (I) concentrations were determined after an overnight fast (F) and upto 60 minutes during OGTT with glucose 75g in 12 normal (N), 14 with impaired glucose tolerance (IGT) and 41 subjects with Type 2 DM. First phase insulin secretion (Δ Insulin) was determined as a percentage rise from baseline 100x (Peak-Basal)/Basal. Insulin sensitivity was determined as FI x FG (mUxmM/L). Results: FG were normal (7.0 mM/L in Type 2 DM. FI x FG and ? insulin were 35 ± 4 and 389 ± 89% in N; 77 ± 5 and 254 ± 65% in IGT; and 235 ± 19 and 95 ± 15% in Type 2 DM. Significant negative correlations were noted between ? insulin one hand and FI x FG on the other amongst all subjects [p < 0.0001 for all correlations]. Conclusion: Decline of 1st phase insulin secretion in IGT and Type 2 DM may be attributed to inhibited release of depleted insulin stores in the β Cells induced by impaired glucose entry due to insulin resistance, and is unlikely to be caused by glucose toxicity in IGT in presence of fasting euglycemia.

BACKGROUND In the UK Prospective Diabetes Study (UKPDS), many subjects maintained glycemic goal (HbA(1c) < 7.0%) at 9 years, showing that beta-cell function was preserved and that the initial decline in beta-cell function recovered with sulphonylureas. Moreover, obese subjects using high daily doses of insulin for several years rarely require insulin or oral hypoglycemic agents to maintain their glycemic goal following weight loss achieved by gastric bypass surgery. Thus, declining beta-cell function during the course of type 2 diabetes mellitus (T2DM) is neither universal nor permanent. OBJECTIVE To assess beta-cell function in morbidly obese subjects before insulin withdrawal and on attaining the glycemic goal with weight loss and oral agents. MATERIALS AND METHODS Serum C-peptide (CPEP) and glucose (G) concentrations were determined up to 180 min during an oral glucose tolerance test (OGTT) with 75 glucose in 10 obese men with T2DM, before insulin withdrawal, and on achieving the glycemic goal with metformin, glimepiride, and weight loss. Ten age-matched healthy men participated as controls. Cumulative responses (CR) of CPEP and G were calculated by adding differences between the level at each time-period during OGTT and fasting (F) concentration. beta-Cell function was expressed as the FCPEP as well as the insulinogenic index (CRCPEP/CRG). Insulin sensitivity was determined as FCEP x FG. RESULTS FCPEP was decreased, though still present, prior to insulin withdrawal. Moreover, on attaining the glycemic goal over 6-9 months, FCPEP, CRPEP/CRG, and FCPEP x FG improved markedly (P < 0.001). CONCLUSION Decline in beta-cell function in morbidly obese T2DM may not be progressive and is reversible on improving insulin sensitivity and on eliminating the inhibition by exogenous insulin.

The data regarding comparison of efficacy of metformin with glimepiride, newest Sulfonylurea, or with the use of both drugs in combination with insulin is rare in the literature. Therefore, we assessed the daily insulin dose, hypoglycemic events and body weight on achieving desirable glycemic control after addition of insulin, to glimepiride 8 mg and/or metformin 2500 mg, in subjects with type 2 DM manifesting lapse of glycemic control.S.C. insulin Novolog Mix [70/30], pre-supper was initiated in 12 subjects on metformin, 14 subjects on glimepiride, and 12 subjects receiving both drugs, with HbA1C7.5% and eight subjects receiving placebo. Insulin dose was increased by 4 U at weekly interval until fasting blood sugar [FBS] between 6.6 and 8 mM/l was attained and then further titrated by 2 U every week to attain and maintain FBS between 4.5 and 6.7 mM/l over the next 4 months. The comparisons were conducted between these groups for HbA1C, the daily insulin dose, body weight noted at the end of this study period as well as the hypoglycemic episodes per patient during the last 4 weeks of the study period.HbA1C levels were7.0% in all subjects at the end of the study. The daily insulin dose (units), total and per kg/BW was significantly lower [p0.001] with metformin (51 +/- 5, 0.51 +/- 0.10), glimepiride (40 +/- 4, 0.42 +/- 0.09) as well as with both drugs (23 +/- 7, 0.21 +/- 0.07) in comparison to placebo (82 +/- 10, 0.82 +/- 0.12). The insulin dose was also significantly lower [p0.05] in subjects on both drugs than subjects receiving them individually. Weight gain was less [p0.001] with metformin [2.5 +/- 0.74 kg], glimepiride [2.3 +/- 0.7 kg], and both drugs [2.2 +/- 0.61 kg] in comparison to placebo [5.2 +/- 1.4 kg] whereas the hypoglycemic episodes were lesser with metformin (3.8 +/- 1.2) and glimepiride (3.3 +/- 0.9) and least with both drugs (2.5 +/- 0.6) in comparison to placebo (5.2 +/- 1.0).Glimepiride and metformin are effective individually in achieving a glycemic goal with a less daily insulin dose, weight gain, and hypoglycemic episodes in comparison to insulin monotherapy in subjects with type 2 diabetes mellitus with further marked reduction in these parameters when used concurrently.

BACKGROUND: In subjects with type 2 diabetes mellitus, glycemic control deteroriates while patients use sulfonylurea drugs during the course of the disease. Adjunctive therapy with insulin at this stage requires a lesser daily insulin dose in comparison with insulin monotherapy while restoring desirable glycemic control. However, data regarding direct comparison between various sulfonylureas in this regard are lacking. OBJECTIVE: To examine comparative efficacies of adjunctive therapy with insulin in subjects with type 2 diabetes manifesting lapse of glycemic control while receiving various individual sulfonylurea drugs. METHODS: Four groups of 10 subjects, each presenting with glycosylated hemoglobin (HbA1C) >8.0% while using either tolazamide, glyburide, glipizide Gastrointestinal Therapeutic System (GITS), or glimepiride, were recruited. Two from each group were randomized to receive placebo; the others continued the same drug. Pre-supper subcutaneous 70 NPH/30 regular insulin was initiated at 10 units and gradually increased and adjusted as necessary to attain fasting blood glucose levels between 80 and 120 mg/dL and maintain the same range for 6 months. Fasting plasma glucose, plasma C-peptide, and HbA1C concentrations were determined prior to the addition of insulin and at the end of the study. Daily insulin dose and changes in body weight (BW) were noted at the end of the study, and the number of hypoglycemic events during the last 4 weeks of the study was determined. RESULTS: Daily insulin dose (units/kg BW), weight gain, and number of hypoglycemic events were significantly lower (p < 0.01) in subjects receiving sulfonylureas in comparison with placebo. However, the daily insulin dose alone was significantly lower (p < 0.05) with glimepiride (0.49 ± 0.10; mean ± SE) than with other sulfonylureas (tolazamide 0.58 ± 0.12, glyburide 0.59 ± 0.12, glipizide GITS 0.59 ± 0.14). Finally, a significant correlation (r = 0.68; p < 0.001) was noted between suppression of plasma C-peptide level and the daily insulin dose among all participants. CONCLUSIONS: By lowering the daily insulin dose, sulfonylurea drugs appear to improve the sensitivity of exogenous insulin in subjects with type 2 diabetes mellitus manifesting lapse of glycemic control. Moreover, glimepiride appears to possess a greater insulin-sparing property than other sulfonylureas.

Malnutrition with muscle wasting, weight loss, and decreased immunogenicity is a hallmark of Acquired Immune Deficiency Syndrome (AIDS). Several anabolic agents have been utilized for retarding or preventing progressive wasting with limited success. However, insulin, with its most effective anabolic properties, has not been tried in an attempt to prevent or reverse cachexia in AIDS or any other wasting disorders. We report here the effect of using subcutaneous (s.c.) daily administration of insulin 0.3 U/kg (BW) for 6 months in a subject with AIDS. We noted a marked weight gain, improvement in metabolic profiles, that is, lowering of triglyceride, liver enzymes, glycohemoglobin concentrations, as well as 24-hour urinary excretion of urea nitrogen, protein, and creatinine suggestive of positive energy balance. Simultaneously, a marked rise in CD4 counts and an improvement in the thyroid hormone profile were also noted. A deterioration in these parameters occurred during the period of insulin withdrawal following completion of the study protocol. Resumption of insulin administration, on patient's request, once again resulted in the marked improvement similar to that noted during the study period. No adverse effects, including hypoglycemic episodes, were noted during either phase of insulin administration. The possibility that insulin administration may improve the wasting associated with AIDS may warrant further evaluation.

OBJECTIVE To judge how reliably patients perform capillary blood glucose testing over time with recurrent practice at home and to assess if a clinic glucose meter is an acceptable alternative to the clinical laboratory for monitoring patient performance. RESEARCH DESIGN AND METHODS We compared capillary blood glucose readings obtained by patients with their own equipment and the venous blood glucose determinations by the clinical laboratory at three biweekly visits during the initial phase in 40 subjects attending the diabetes clinic at the Veterans' Affairs Medical Center in Phoenix, Arizona. We also compared patient-generated readings using their own equipment and the readings obtained by the clinic glucose meter and strips at five weekly visits during the second phase in 11 subjects who continued further participation. Error grid analysis was used for both comparisons. Capillary blood glucose readings obtained with clinic glucose meter and strips on one hand were correlated with venous blood glucose levels determined by the clinical laboratory. RESULTS During the initial phase, 30 subjects consistently obtained clinically acceptable comparisons (zone A on the error grid, i.e., within 20% of the laboratory value) or improved over time, 9 subjects showed deterioration, and 1 subject failed to obtain zone A results on any of the visits. Three subjects who had consistently obtained zone A results during the initial phase maintained their performance, whereas eight subjects who had failed to achieve zone A values by the end of the initial phase gradually improved and ultimately achieved zone A values by the end of the study. A highly significant correlation was noted between clinic meter readings and laboratory values (r = 0.93, P < 0.00001). CONCLUSIONS Clinically acceptable user proficiency in capillary blood glucose testing can be maintained in most subjects, with recurrent intensive education during follow-up clinic visits. Therefore, we recommend that these comparisons be performed and patient's technique be observed at each visit to monitor their performance. The clinic glucose meter is a suitable alternative to a clinical laboratory for user proficiency checks.

To investigate whether the mechanism of increased glycation in acquired immunodeficiency syndrome (AIDS) is due to an alteration in a circulatory plasma enhancer.We assessed glycation of serum protein and hemoglobin in patients with AIDS without altered carbohydrate metabolism. Fasting concentrations of glucose, ethanol, vitamin E, fructosamine, hemoglobin, hemoglobin A1c (A1C), and partial pressure of alveolar oxygen (PAO2) were determined in 50 men with AIDS and in 25 age-matched healthy men in whom normal glucose tolerance was established by oral glucose tolerance tests.Fasting serum glucose was not significantly different between the men with AIDS (87 +/- 4 mg/dL) and the healthy male volunteers (84 +/- 6 mg/dL); however, A1C (6.9 +/- 0.2%) and serum fructosamine levels (288 +/- 15 micromol/L) were significantly higher (P.01) in the patients with AIDS than in the normal subjects (A1C, 5.6 +/- 0.1%; fructosamine, 204 +/- 14 micromol/L). Moreover, both A1C and fructosamine concentrations were significantly higher (P.01) in the patients with AIDS than in the normal subjects divided into subgroups on the basis of fasting plasma glucose concentrations (70 to 79 mg/dL, 80 to 89 mg/dL, and 90 to 99 mg/dL). None of the study participants had anemia (hemoglobin12 g/dL) or hypoxia (PAO295 mm Hg), and serum ethanol was undetectable. Furthermore, vitamin E concentrations were not significantly different between the patients with AIDS (25 +/- 3 mg/L) and the normal subjects (22 +/- 4 mg/L).On the basis of this study, glycation of some circulating proteins appears to be enhanced in AIDS and may be induced by an undetermined plasma enhancer, inasmuch as known circulating factors promoting glycation were absent.

1. Study Design, Patients and Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288 2. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291 3. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291 4. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292

The exact mechanism of the efficacy of glimepiride in the achievement of glycemic control has not yet been clearly defined.This study was conducted to examine the influence of glimepiride on insulin secretion and sensitivity in patients with type 2 diabetes mellitus (DM) of recent onset.This 24-week, open-label, controlled trial was conducted at the Division of Endocrinology and Metabolism, Veterans Affairs Medical Center (Phoenix, Arizona). Study participants were aged 32 to 75 years and had recent-onset (established by a short duration of symptoms 6 weeks to 6 months prior to the study) type 2 DM, or were age-matched healthy volunteers (control group). In the diabetic patients, glimepiride tablets were administered orally, initially at 2 mg once daily in the morning, with the dosage increased by 1 mg every 2 weeks until fasting plasma glucose (FPG) decreased to 6.7 mmol/L; the dosage was then maintained for the remainder of the 24-week study period. Oral glucose tolerance tests (OGTTs) were conducted in the control group and before treatment and at 24 weeks after the achievement and maintenance of glycemic control (glycosylated hemoglobin7.0%) in the diabetic group. For OGTT, plasma insulin and glucose levels were determined after the subjects fasted overnight and then at every 15 minutes for 2 hours after glucose challenge.Fourteen diabetic men (mean [SEM] age, 50 [6] years; range, 32-75 years) and 10 male healthy controls (mean [SD] age, 48 [5] years; range, 30-68 years) were enrolled. In the DM group, FPG decreased significantly after treatment ( P0.001); fasting plasma insulin was markedly elevated before treatment (P0.001 vs controls) and decreased after treatment ( P0.01) but did not normalize; first-phase insulin secretion was markedly inhibited before treatment ( P0.001 vs controls) and normalized after treatment ( P0.001) total insulin secretion significantly improved after treatment ( P0.01) but did not normalize. Finally, the pretreatment insulin sensitivity index decreased significantly (P0.01) after treatment and normalized in 6 of 14 patients (42.9%) with type 2 DM.In this study, glimepiride achieved desirable glycemic control in patients with recent-onset type 2 DM through improvement in insulin secretion and sensitivity.

BACKGROUND: Home blood glucose (HBG) monitoring has become an established practice in management of diabetes mellitus. However, it is unlikely to affect glycemic control unless the patients can and do act promptly, i.e., adjust insulin dose or type, in response to blood glucose readings. Moreover, the patients treated with diet and/or oral drugs are unable to take a prompt similar action. Finally, patients with type 2 diabetes rarely manifest extreme excursions of diurnal glycemia; however, the data in this regard are sparse. AIMS: This study assessed the influence of (1) HBG testing, (2) home urine glucose (HUG) testing, and (3) no testing (NT) on metabolic control, i.e., fasting plasma glucose, glycohemoglobin (HbA 1C ), and lipids, in 42 patients with type 2 diabetes. METHODOLOGY: All subjects underwent each testing phase lasting 4 months in a randomized sequence. HBG or HUG testing was performed four times daily, prior to meal and at bedtime. RESULTS: No significant differences were observed in fasting plasma glucose and HbA concentrations 1C or lipid profiles at the end of each testing. CONCLUSION: It is apparent that HBG testing alone without an opportunity for prompt intervention, i.e., insulin administration, may be a wasteful exercise. We recommend an efficient cost-saving strategy of HBG testing with visual strips alone in patients not receiving insulin, only in the presence of symptoms of hypoglycemia or hyperglycemia, and at the onset of acute illness.