Effect of strict blood glucose control on residual B-cell function in insulin-dependent diabetics

Summary In 14 insulin dependent diabetics past their initial remission period B-cell function was evaluated using a test meal before and after 1 week of strict blood glucose control, and again 3 weeks later when the patients were outpatients on conventional therapy. Eight patients with fasting C-peptide above 0.07 nmol/l improved their B-cell function significantly (p<0.05) during the period of strict blood glucose control. However, the improvement was of short duration and was absent 3 weeks later in most patients. Six patients with fasting C-peptide below or equal to 0.07 nmol/l had no significant improvement in B-cell function during the period of strict control. The study shows that B-cell function and degree of blood glucose control are related in patients with fasting C-peptide above 0.07 nmol/l, and that B-cell function can change within days.     

Human leukocyte interferon treatment of two children with insulin dependent diabetes

Summary Two patients with newly diagnosed insulin dependent diabetes mellitus were treated with human leukocyte interferon based on the hypothesis that the diabetes was induced by an active viral infection in the pancreatic islets and could be arrested. High peak levels of serum interferon were achieved (100–200 U/ml) with minimal systemic side effects. There was no sustained therapeutic benefit as measured by increased production of endogenous insulin, or of C-peptide, or by a lower requirement for exogenous insulin. Further trials with interferon treatment should be undertaken only if evidence of active viral infection (culture, antigen detection) can be associated with insulin dependent diabetes onset and these markers followed during treatment.     

Enhancement of B-cell secretion by blood glucose normalization in type 2 diabetes is associated with fasting C-peptide levels

OBJECTIVES: To investigate (i) the variability of beneficial effects achieved by short-term near-normalization of blood glucose in type 2 diabetes patients, and (ii) the relationship of beneficial effects to individual characteristics of diabetes. DESIGN: Arginine-induced insulin and glucagon release tested at two glucose levels before and after 3 days of intensive insulin treatment. SETTING: The Department of Endocrinology and Diabetology, Karolinska Hospital, Stockholm, Sweden. SUBJECTS: Type 2 diabetes patients with poor metabolic control sampled from an area-based population of diabetes patients. RESULTS: Levels of fasting blood glucose declined from 15.0 +/- 0.9 to 8.5 +/- 0.7 mmol L-1, C-peptide from 0.81 +/- 0.06 to 0.49 +/- 0.05 nmol L-1 and percent proinsulin (of total IRI) from 7.8 +/- 1.0 to 3.2 +/- 0.6%. At comparable glucose levels arginine-induced insulin secretion was enhanced 46.3 +/- 19.5% (range -36 to 220%). Enhancement correlated with extent of blood glucose normalization and also with fasting C-peptide levels and with overweight. Arginine-induced glucagon secretion was nonsignificantly depressed (17.2 +/- 7.4%, range -59 to 29%). Insulin sensitivity assessed by M:I ratio was increased by a median of 95%. CONCLUSIONS: In type 2 diabetes patients reversibility of the effects of poor metabolic control on B-cell function is variable. Variability is related to B-cell mass in individual patients with type 2 diabetes.     

Prevalence of diabetes mellitus,coronary heart disease and hypertension in the families of insulin dependent and insulin independent diabetics

Summary During an epidemiological study concerning the fate of diabetics in Warsaw, 2,356 subjects (aged 35–68 years with duration of diabetes mellitus of 3–11 years) were investigated with particular relevance to the presence of diabetes mellitus, coronary heart disease, and hypertension in their parents and siblings. Diabetics were classified into the following groups: insulin dependent, insulin independent nonobese, insulin independent obese, and a group in whom the distinction between insulin dependence and insulin independence was unclear. The findings in these groups were compared with the frequencies of these diseases in a random sample of the general population. There was an excess of diabetes in close relatives of all the diabetic groups. This was highest for insulin independent non-obese diabetics. There was no difference in the prevalence of coronary heart disease and hypertension in close relatives of insulin dependent diabetics when compared with the general population, but these were twice as prevalent in close relatives of the insulin independent non-obese group. Obese insulin independent diabetics reported a similar excess of coronary heart disease and hypertension in siblings, but the excess was less marked in parents. The prevalence of these diseases in families of probands with unclassified diabetes was intermediate between the other two groups. These results demonstrate an aggregation of diabetes mellitus with coronary heart disease and hypertension in families of insulin independent non-obese diabetics. This provides further evidence for heterogeneity in diabetes mellitus.     

The predictive capability of the glycaemic response to spaghetti in non-insulin dependent (NIDDM) and insulin dependent (IDDM) diabetic subjects

To evaluate the predictive capability of the postprandial blood glucose response after consumption of a starch-rich meal, we compared the glycaemic effects of spaghetti (60 g) taken alone and with bolognese sauce (167 g). The study was carried out in both NIDDM (n = 6) and IDDM (n = 6) subjects. The latter had achieved normoglycaemia 120 min prior to the test meal by means of an artificial pancreas (Biostator) which provided constant insulinaemia during the observation period of 4 h. We found that the areas of blood glucose (above basal) were identical irrespective of whether spaghetti was taken alone or as part of a mixed meal in both NIDDM (484 +/- 154 mmol l-1 240 min-1 vs. 393 +/- 126 mmol l-1 240 min-1) and IDDM subjects (610 +/- 143 mmol l-1 240 min-1 vs. 770 +/- 135 mmol l-1 240 min-1). The insulin levels were identical in the IDDM diabetics. By contrast, the mixed meal caused a more marked insulinaemic response than spaghetti per se in the NIDDM subjects (3187 +/- 637 mU l-1 240 min-1 vs. 1940 +/- 235 mU l-1 240 min-1; P less than 0.05). In conclusion, the predictive capability of the glycaemic response to spaghetti was good in both IDDM and NIDDM diabetic subjects, at least under the conditions of the present study.     

Improvement of metabolic control in insulin dependent diabetics treated with the α-glucosidase inhibitor Acarbose for two months

Summary Acarbose, an -glucosidase inhibitor, delays starch digestion and inhibits intestinal sucrase and maltase activity. Twenty-eight insulin dependent diabetics were given Acarbose (3×100 mg daily) over a two month period, preceded and followed by a two month placebo period. Acarbose reduced post-break-fast and post-dinner blood glucose values by 25% (p <0.001) and 24% (p<0.05) respectively. It also significantly reduced mean daily blood glucose by 18% (p < 0.05) and mean amplitude of glycaemic excursions from 8.0±0.6 to 5.5±0.4 mmol/l (p<0.0005). Weight did not change significantly. Daily caloric and carbohydrate intake remained constant throughout the study while insulin requirements decreased slightly but significantly. Out of the 28 patients, 18 had absent while ten had slight residual B cell function as assessed by plasma C-peptide measurements. Treatment with Acarbose did not significantly affect residual B cell function. The beneficial effect of Acarbose on blood glucose control was seen in patients both with and without residual B cell secretion. The major side-effect was flatulence which was never severe enough to interrupt treatment, but led to a 50% reduction of the dose in one patient. It is concluded that Acarbose represents a useful additional means of improving metabolic control in insulin dependent diabetics.     

Decreased insulin action and insulin secretion predict the development of impaired glucose tolerance

Summary The relative importance of insulin resistance and abnormal insulin secretion as risk factors for the development of impaired glucose tolerance (IGT) is controversial. Few prospective data are available on metabolic precursors of IGT. We examined the relation of fasting serum insulin level (as a marker of insulin resistance) and change in insulin/glucose ratio (ΔI ₃₀/ΔG₃₀) over the first 30 min after glucose ingestion (as a marker of insulin secretion) as predictors of the 7-year development of IGT in 839 Mexican Americans and non-Hispanic whites with normal glucose tolerance at baseline from the San Antonio Heart Study. IGT eventually developed in 148 subjects. When modelled separately, fasting serum insulin (odds ratio (OR)=2.60,95 % confidence interval (CI)=1.58,4.28,p<0.005), but not ΔI ₃₀/ΔG₃₀ (OR=0.80, 95 % CI=0.50,1.27,p=0.339) predicted the development of IGT. However, when both variables were included in the same logistic regression model, fasting serum insulin (OR=3.50, 95 % CI=1.97,6.21,p<0.001) and low ΔI ₃₀/ΔG₃₀ (OR=0.48, 95 % CI=0.28,0.82,p=0.008) both predicted IGT. These results were basically unchanged after further adjustment for obesity, body fat distribution and fasting plasma glucose level. We conclude that both decreased insulin secretion (as assessed by low ΔI ₃₀/ΔG₃₀) and increased insulin resistance (as assessed by fasting serum insulin) predict the development of IGT and are thus early precursors of non-insulin-dependent diabetes mellitus; further studies of insulin secretion should take into account the level of basal insulin resistance.     

The effect of Ramadan fasting on glycaemic control in insulin dependent diabetic patients: A literature review

Background

Ramadan fasting is one of the five pillars of Islam. People with diabetes are exempted from fasting according to Islamic rules. However, many people with diabetes wish to fast. Physicians are asked frequently by their patients about their ability to fast and the possible impact of fasting on their glycaemic control. Studies about the effect of Ramadan on people with insulin-treated diabetes are scarce. This review aims to provide clinicians with the best recommendations for their patients with insulin-treated diabetes who wish to fast.

The glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals is increased in patients with Type 2 (non-insulin-dependent) diabetes mellitus

Summary Considerable disagreement exists regarding the levels of immunoreactive glucose dependent insulinotropic polypeptide in patients with Type 2 (non-insulin-dependent) diabetes mellitus. Glucose dependent insulinotropic polypeptide levels were therefore studied during oral glucose and mixed meal tolerance tests in normal subjects (n=31) and newly presenting previously untreated patients with Type 2 diabetes mellitus (n=68). The tests were performed in random order after overnight fasts and blood samples were taken at 30 min intervals for 4 h. During the oral glucose tolerance test plasma glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a fasting value of 20±3 pmol/l to a peak of 68±5 pmol/l at 30 min and in the Type 2 diabetic patients from a similar fasting level of 27±3 pmol/l to a higher peak value of 104±6 pmol/l at 30 min (p<0.001). Glucose dependent insulinotropic polypeptide levels were significantly higher in the diabetic patients compared with the normal subjects from 30–90 min (p<0.01–0.001) following oral glucose. During the meal tolerance test glucose dependent insulinotropic polypeptide levels increased in the normal subjects from a pre-prandial value of 22±4 pmol/l to a peak of 93±6 pmol/l at 90 min and in the Type 2 diabetic patients from a similar basal level of 25±2 pmol/l to a higher peak of 133±7 pmol/l at 60 min. Glucose dependent insulinotropic polypeptide concentrations were significantly higher in Type 2 diabetic patients compared with the normal subjects at 30 min (p<0.001), 60 min (p<0.01) and from 210–240 min (p<0.05) during the meal tolerance test. The groups were subdivided on the basis of degree of obesity and glucose dependent insulinotropic polypeptide concentrations were still higher in the diabetic subgroups compared with the normal subjects matched for weight. Type 2 diabetes mellitus is associated with an exaggerated glucose dependent insulinotropic polypeptide response to oral glucose and mixed meals which is independent of any effect of obesity.     

Assessment of insulin sensitivity and secretion with the labelled intravenous glucose tolerance test: improved modelling analysis

Summary A new modelling analysis was developed to assess insulin sensitivity with a tracer-modified intravenous glucose tolerance test (IVGTT). IVGTTs were performed in 5 normal (NGT) and 7 non-insulin-dependent diabetic (NIDDM) subjects. A 300 mg/kg glucose bolus containing [6,6-²H₂]glucose was given at time 0. After 20 min, insulin was infused for 5 min (NGT, 0.03; NIDDM, 0.05 U/kg). Concentrations of tracer, glucose, insulin and C-peptide were measured for 240 min. A circulatory model for glucose kinetics was used. Glucose clearance was assumed to depend linearly on plasma insulin concentration delayed. Model parameters were: basal glucose clearance (Cl_b), glucose clearance at 600 pmol/l insulin concentration (Cl₆₀₀), basal glucose production (P_b), basal insulin sensitivity index (BSI = Cl_b/basal insulin concentration); incremental insulin sensitivity index (ISI = slope of the relationship between insulin concentration and glucose clearance). Insulin secretion was calculated by deconvolution of C-peptide data. Indices of basal pancreatic sensitivity (PSI_b) and first (PSI₁) and second-phase (PSI₂) sensitivity were calculated by normalizing insulin secretion to the prevailing glucose levels. Diabetic subjects were found to be insulin resistant (BSI: 2.3 ± 0.6 vs 0.76 ± 0.18 ml · min^–1· m^–2· pmol/l^–1, p < 0.02; ISI: 0.40 ± 0.06 vs 0.13 ± 0.05 ml · min^–1· m^–2· pmol/l^–1, p < 0.02; Cl₆₀₀: 333 ± 47 vs 137 ± 26 ml · min^–1· m^–2, p < 0.01; NGT vs NIDDM). P_b was not elevated in NIDDM (588 ± 169 vs 606 ± 123 μmol · min^–1· m^–2, NGT vs NIDDM). Hepatic insulin resistance was however present as basal glucose and insulin were higher. PSI₁ was impaired in NIDDM (67 ± 15 vs 12 ± 7 pmol · min^–1· m^–2· mmol/l^–1, p < 0.02; NGT vs NIDDM). In NGT and in a subset of NIDDM subjects (n = 4), PSI_b was inversely correlated with BSI (r = 0.95, p < 0.0001, log transformation). This suggests the existence of a compensatory mechanism that increases pancreatic sensitivity in the presence of insulin resistance, which is normal in some NIDDM subjects and impaired in others. In conclusion, using a simple test the present analysis provides a rich set of parameters characterizing glucose metabolism and insulin secretion, agrees with the literature, and provides some new information on the relationship between insulin sensitivity and secretion. [Diabetologia (1998) 41: 1029–1039] Received: 17 September 1997 and in final revised form: 28 April 1998     

Persistent insulin secretion,assessed by plasma C-peptide estimation in long-term juvenile diabetics with a low insulin requirement

Summary In order to investigate whether patients with long-standing juvenile diabetes mellitus (onset of diabetes before the age of 30) and a low daily insulin requirement (< 0.50 units/kg body weight) still have functioning B-cells, plasma C-peptide was determined after stimulation (OGTT and glucagon/ tolbutamide) in 64 patients with diabetes of more than 18 years' duration (mean 31 years). Measurable endogenous insulin production was found in 24% of the patients. The prevalence of severe retinopathy was lower in the secretors than in the non-secretor group. There was no difference in insulin antibody concentration between the two groups. Furthermore, the insulin requirement in the secretor group was relatively constant during the course of diabetes. Metabolic control was similar in both groups. It is concluded that a persisting but low activity of endogenous insulin production can be found in many long-term juvenile diabetics with a low insulin requirement, while others without any residual betacell function develop a low insulin requirement for unknown reasons.     

Serum insulin,insulin antibodies and insulin requirement in the first period of insulin treatment in non-insulin resistant diabetics

Summary Twelve insulin-sensitive diabetics were studied for 200 days after the initiation of mixed beef-pork NPH insulin. Normalization of the fasting blood glucose was not accompanied by any elevation in the pre-treatment fasting immunoreactive insulin level. Insulin antibodies appeared in 2 patients on the second week of insulin treatment, in 6 others within 87 days. In 4 patients no antibodies were found 200 days after the start of insulin. The appearance of antibodies was accompanied in two patients by a decrease in insulin requirement, in others there was no change. When antibodies were present, the total maximum insulin binding capacity was 4 to 12 U/1, but the total insulin constituted only 3 to 36% of the binding capacity. Insulin wastage caused by the destruction of the immune complexes was calculated to be 0.35 to 5.6 U/die only, and this explains the negligible effect of insulin antibodies on insulin requirement in non-resistant patients. Presented at the 10th Annual Meeting of the European Association for the Study of Diabetes in Jerusalem, September 11–13, 1974.     

A rapid increase in beta-cell function by multiple insulin injections in type 2 diabetic patients is not further enhanced by prolonging treatment

OBJECTIVE: Intensive insulin treatment in type 2 diabetes can improve beta-cell function. It is not known which duration of treatment achieves maximal improvement. We addressed this question in type 2 diabetic patients who displayed features of 'secondary failure'. RESEARCH DESIGN AND METHOD: Ten patients were randomized to multiple insulin injection (MI) therapy for 9 weeks. Another 10 patients started with bedtime insulin (BTI) and continued their peroral medication. Following 9 weeks of treatment, patients on MI switched to BTI and glibenclamide. RESULTS: Three days of MI led to a decrease in fasting proinsulin/insulin ratio, 0.43 +/- 0.20 vs. 0.29 +/- 0.11, P=0.01 and an increase in glucagon-stimulated C-peptide over baseline, 0.77 +/- 0.43 vs. 1.28 +/- 0.44 nmol L-1, P 0.02. Nine weeks of MI treatment successively decreased fasting and nonfasting blood glucose in parallel with increasing insulin dosage. Initial improvements in secretion parameters were upheld but not further enhanced, the 9 week proinsulin/insulin ratio being 99 +/- 23% and that of glucagon-stimulated C-peptide being 95 +/- 24% of the values obtained after 3 days of treatment. Eight weeks after termination of MI there persisted a total weight gain that tended to be larger than after continuous peroral medication with BTI. CONCLUSION: Improvement of insulin secretion by intensive insulin treatment is rapidly gained with no further effect obtained after a longer treatment period. This finding, as well as undesirable effects of MI on body weight, argues against prolonged MI treatment as a prelude to other therapeutic regimens in type 2 diabetic patients.     

The relationships between thyroid-stimulating hormone level and insulin resistance,glucose effectiveness,first- and second-phase insulin secretion in Chinese populations

Increased insulin resistance (IR); decreased glucose effectiveness (GE); and both first-and second phase of insulin secretion (FPIS, SPIS) have always been important factors for the development of type 2 diabetes. Therefore, in this study, we evaluated the relationships between thyroid-stimulating hormone (TSH) and these 4 factors in adult Chinese.We randomly enrolled 24,407 men and 24,889 women between 30 and 59 years old. IR, FPIS, SPIS and GE were measured with the equations built by our group.

• IR = log (1.439 + 0.018 × sex - 0.003 × age + 0.029 × BMI - 0.001 × SBP + 0.006 × DBP + 0.049 × TG - 0.046 × HDLC - 0.0116 × FPG) × 10 ^3.333
• FPIS = 10 [1.477 - 0.119 × FPG + 0.079 × BMI - 0.523 × HDLC]
• SPIS = 10 [-2.4 - 0.088 × FPG + 0.072 × BMI]
• GE = (29.196 - 0.103 × age - 2.722 × TG - 0.592 × FPG) ×10 ⁻³

The t test was performed to evaluate the differences between normal and diabetic groups. To evaluate the differences of the mean values of the 4 groups, from the highest to the lowest levels of TSH, we used a one-way analysis of variance.Age, high density lipoprotein-cholesterol and GE were higher in women. On the other hand, body mass index, blood pressure, low density lipoprotein-cholesterol, triglyceride, FPIS, SPIS and IR were higher in men. TSH was positively related to IR, FPIS, and SPIS and negatively related to GE. According to the r values, the tightest relationship was between TSH and IR, followed by GE, FPIS and SPIS.In conclusion, our data showed that IR, FPIS, and SPIS were positively related to the TSH level in middle-aged Chinese, whereas GE was negatively related. In both genders, IR had the tightest association followed by GE, FPIS, and SPIS.     

Fat-induced changes in mouse pancreatic islet insulin secretion,insulin biosynthesis and glucose metabolism

Insulin secretion, insulin biosynthesis and islet glucose oxidation were studied in pancreatic islets isolated from fat-fed diabetic mice of both sexes. Insulin secretion from isolated islets was studied after consecutive stimulation with -ketoisocaproic acid + glutamine, glucose, forskolin, and 12-O-tetradecanoylphorbol 13-acetate. Glucose-induced insulin secretion was impaired in islets from fat-fed mice. This was associated with a reduction of approximately 50% in islet glucose oxidation. Islet insulin secretion stimulated by the non-carbohydrate secretagogues tended to be higher in the fat-fed mice, but a statistically significant effect was not observed. Pancreatic insulin content was reduced by 50%, whereas the islet insulin and DNA content was unchanged after fat feeding. Proinsulin mRNA was reduced by 35% in islets from fat-fed mice, and was associated with a reduction of approximately 50% in glucose-stimulated (pro)insulin biosynthesis. It is concluded that the insulin secretory response of islets isolated from fat-fed mice is similar to the secretory pattern known from human type 2, non-insulin-dependent diabetics, and that a defect in islet glucose recognition, resulting in decreased glucose oxidation, may be responsible for the observed insulin secretory and biosynthetic defects seen after glucose stimulation.     

Dexamethasone treatment fails to increase arginine-induced insulin release in healthy subjects with low insulin response

Summary We have compared insulin responses to L-arginine before and during dexamethasone treatment in healthy subjects, previously classified as subjects with either high or low insulin response according to a standardized glucose infusion test. Arginine stimulation was administered as a 150 mg/kg bolus followed by 10 mg·kg^–1·min^–1 to six subjects with high insulin response and to seven subjects with low insulin response. Before dexamethasone treatment the incremental insulin level during 0–10 min of arginine was higher in subjects with high (36.5±6.8 U/ml) than in subjects with low response (14.5±2.3 U/ml), p<0.01 for difference. Dexamethasone treatment (6 mg/day for 60 h) markedly enhanced the insulin response to arginine in subjects with high response (+99% 0–30 min) but failed to affect the subjects with low response (+4% 0–30 min). The C-peptide response to arginine exhibited similar differences between groups. Decreased responsiveness to arginine in subjects with low insulin response, especially during dexamethasone treatment, suggests a Beta-cell capacity defect although a decreased potentiating-sensing effect of glucose cannot be completely ruled out.     

Paradoxical inhibition of insulin secretion by glucose in non-insulin-dependent diabetic patients

In young healthy individuals, an i.v. glucose bolus leads to an immediate increase in plasma insulin, whereas in non-insulin-dependent diabetic patients this early response is diminished, lacking or even negative. In the present study, we sought to determine whether negative responses were also present during square-wave glucose stimulation (transition from 18 to 25 mM), whether they represented a decrease in beta-cell secretion, whether they were accompanied by an altered response to arginine (5 gl-arginine bolus), and whether they were a consequence of ageing rather than of diabetes. A group of 12 patients (aged 53±2 years, mean±SE) with non-insulin-dependent diabetes (D) and 12 matched healthy controls (C; aged 47±1 years) were evaluated twice at an interval of 3 months. Other baseline values were body mass index (BMI) 28±1 (D) and 26±1 (C) kg/m², fasting C-peptide 0.85±0.12 (D) and 0.92±0.10(C) nmol/l, and fasting P-glucose 12.3±0.9 (D) and 5.8±0.1 (C) mM,P<0.05. Paradoxical responses (a decrease of two or more times the SD of the analysis within 15 min of increasing the glucose concentration) were seen in five diabetic patients for insulin (22±8%) and in nine diabetic patients for C-peptide (13±3%), but never in the healthy controls. Plasma glucose increased and protein decreased similarly, whether the responses were paradoxical or not. Paradoxial responses were reproduced after three months. Responses to arginine did not correlate with responses to glucose. In summary, in contrast to healthy matched controls, 40–75% of non-insulin-dependent diabetics show a marked initial decrease in beta-cell secretion upon square-wave glucose stimulation. This is probably specific to glucose stimulation, as it did not occur in response to arginine stimulation.     

2型糖尿病家系成员中的胰岛素抵抗与胰岛β—细胞功能状态的研究

目的研究胰岛素抵抗及胰岛紊分泌功能在2型糖尿病(DM)发生、发展中的作用.方法在2型DM家系成员中,对已诊断DM者按病程中位数分组,病程≤4年组153例,＜4年组129例.经口服葡萄糖耐量试验(OGTT),按1999年WHO糖尿病诊断标准,新诊断DM组72例.非DM者按HbAlc分组,HbAlc≤5.5%组78例,HbAlc＜5.5%组110例,计算各组HOMA模型胰岛素抵抗指数(HOMAIR)、β细胞功能指数(HOMAβ)及胰岛素敏感性指数(ISI),与无DM家族史的正常人98例比较.结果除HbAlc≤5.5%组外,家系各组HOMAIR均值高于正常对照,差异有显著性(P＜0.01).家系非DM两组HOMAβ高于正常对照(P＜0.01),DM各组HOMAβ低于正常对照(P＜0.01).结论北京地区2型DM家系中非DM一级亲属的胰岛素抵抗及糖耐量异常可能继发于胰岛素分泌功能异常增高,胰岛素分泌功能降低和胰岛素抵抗是发生糖尿病的主要机制.     

Failure to adequately adapt reduced insulin sensitivity with increased insulin secretion in women with impaired glucose tolerance

Summary To study the islet adaptation to reduced insulin sensitivity in normal and glucose intolerant post-menopausal women, we performed a euglycaemic, hyperinsulinaemic clamp in 108 randomly selected women, aged 58–59 years. Of the 20 women with the lowest insulin sensitivity, 11 had impaired glucose tolerance (IGT) whereas 9 had normal glucose tolerance (NGT). These women together with 15 women with medium insulin sensitivity and 16 women with high insulin sensitivity and NGT were further examined with arginine stimulation at three glucose levels (fasting, 14 and >25 mmol/l). In NGT, the acute insulin response (AIR) to 5 g i. v. arginine at all three glucose levels and the slope_AIR, i. e. the glucose potentiation of insulin secretion, were markedly increased in the women with the lowest insulin sensitivity and NGT compared to those with medium or high insulin sensitivity. In contrast, in low insulin sensitivity, AIR was significantly lower in IGT than in NGT (at glucose 14 mmol/l p=0.015, and at >25 mmol/l p=0.048). The potentiation of AIR induced by low insulin sensitivity in women with NGT was reduced by 74% (AIR at 14 mmol/l glucose) and 57% (AIR at >25 mmol/l glucose), respectively, in women with IGT. Also the slope_AIR was lower in IGT than in NGT (p=0.025); the increase in slope_AIR due to low insulin sensitivity was abolished in IGT. In contrast, glucagon secretion was not different between women with IGT as opposed to NGT. We conclude that as long as there is an adequate beta-cell adaptation to low insulin sensitivity with increased insulin secretory capacity and glucose potentiation of insulin secretion, NGT persists.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - AIR acute insulin response - AGR acute glucagon response