Hypertension in obese and non-obese non-insulin dependent diabetics a matter of regional adiposity?

There is growing evidence that differences in fat distribution can be predictive for differences in the prevalence of metabolic disturbances, cardio-vascular disease, stroke and death, independent of commonly used indices of obesity. This study evaluates regional body fat distribution as a possible main reason for hypertension in obese and non-obese type II diabetics. 42% of normal weight diabetics with abdominal obesity are hypertensive versus 47% of obese diabetics; only 5% hypertension could be found when a lower body segment fat distribution is present. A significant (p less than 0.001) correlation exists between fat mass topography and both systolic (r = 0.49) and diastolic (r = 0.49) blood pressure. This correlation remains true after correction for body mass index and percent glycosylated hemoglobin. These results suggest that localization of fat in the upper body segment should be considered as a additive risk for hypertension.     

HLA antigens in insulin dependent and non-insulin dependent Spanish diabetic patients

HLA-A, -B, -C, -DR and Bw4, Bw6 antigens and Bf and GLO alleles have been studied in a sample of Spanish insulin dependent (IDD) and non-insulin dependent (NIDD) diabetic patients. In IDD's there was no significant increase of B8 and B15; an increase of B18 secondary to that of DR3 has been found. DR4 was also increased in our sample. The GLO-S/DR2 haplotype was found to be decreased in IDD. It was observed that (Aw30)-B18-Cw5-Bw6-DR3-BfF1 is the commonest ID diabetic haplotype in our population. A relationship between DR4 and early IDD onset was also found. No association was found between HLA, or Bf, and age of onset, macroangiopathy, microangiopathy, retinopathy, nephropathy and peripheral or autonomic neuropathy. In NIDD's, DR3 was increased and DR3-non BfF1 and DR3-non B18 RRs were higher than DR3 RR.Aw30 and Cw5 tended to be decreased, although not significantly. These findings further support the hypothesis that several closely linked diabetic susceptibility factors may exist within an HLA haplotype (i.e.: (Aw30)-B18-Cw5-Bw6-DR3-BfF1 in our population) and that all of them may be necessary for developing an IDD form; lack of one or several factors might lead to the acquisition of the NIDD form.     

Effects of weight loss and reduced hyperglycemia on the kinetics of insulin secretion in obese non-insulin dependent diabetes mellitus

Impairment in pancreatic production of insulin, a cardinal feature of noninsulin dependent diabetes mellitus (NIDDM), was quantified and the kinetics of insulin secretion characterized in six obese individuals with NIDDM before and after weight loss (18.0 +/- 3.0 kg, mean +/- SEM) using a validated mathematical model that employs C-peptide as a marker of the in vivo rate of insulin secretion. The metabolic clearance of C-peptide, assessed by decay analysis after bolus injection of biosynthetic human C-peptide, was not changed by weight loss (0.143 +/- 0.009 L/min.m2 vs. 0.137 +/- 0.010 L/min.m2). Kinetic parameters from each individual's decay curve before and after weight loss were used to derive accurate rates of secretion during the basal (postabsorptive) state, an oral glucose tolerance test and two hyperglycemic clamps. Basal rates of insulin secretion declined 20 +/- 5 pmol/min.m2 (96 +/- 15 to 76 +/- 15 pmol/min.m2, P less than 0.05) concomitant with decreases of 6.9 +/- 0.9 mmol/L in fasting serum glucose (13.7 +/- 1.0 to 6.8 +/- 0.7 mmol/L, P less than 0.05), 60 +/- 14 pmol/L in serum insulin (134 +/- 30 to 74 +/- 15 pmol/L, P less than 0.05), and 0.15 +/- 0.03 pmol/ml in plasma C-peptide (0.67 +/- 0.11 to 0.52 +/- 0.08 pmol/ml, P less than 0.05) concentrations. As expected, weight loss resulted in improved glucose tolerance as measured by the glycemic profiles during the oral glucose tolerance test (P less than 0.05 analysis of variance). The insulin secretory response before weight loss showed a markedly reduced ability to respond appropriately to an increase in the ambient serum glucose. After weight loss, the pancreatic response was more dynamic (P less than 0.05, analysis of variance) and parralleled the moment-to-moment changes in glycemia. Insulin production above basal doubled (11.2 +/- 3.2 to 24.5 +/- 5.8 nmol/6h.m2, P less than 0.05) and peak rates of insulin secretion above basal tripled (55 +/- 16 to 157 +/- 32 pmol/min/m2, P less than 0.05). To assess the beta-cell response to glucose per se and the changes associated with weight reduction, two hyperglycemic clamps were performed at steady state glucose levels in the range characteristic of individuals with severe NIDDM. At a fixed glycemia of 20 mmol/L, average rates of insulin secretion increased almost 2-fold with treatment (161 +/- 41 to 277 +/- 60 pmol/min.m2, P less than 0.05). At an increment of 6 mmol/L glucose above prevailing fasting glucose levels, the average rate of insulin secretion increased 53% (120 +/- 21 to 183 +/- 39 pmol/min.m2, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)     

Morning versus bedtime isophane insulin in type 2 (non-insulin dependent) diabetes mellitus.

Morning versus bedtime administration of NPH insulin was compared in 12 subjects with Type 2 diabetes and overt fasting hyperglycaemia. Subjects were studied at baseline (diet alone) and after 2 months on each of the two insulin programmes in a random crossover design, in which dosage was increased until at least one daily preprandial blood glucose was consistently in the range of 3.9 to 6.0 mmol l-1. Mean (+/- SEM) daily total insulin dosage was equivalent for the morning (0.36 +/- 0.03 units kg-1) and for the bedtime (0.37 +/- 0.03 units kg-1) insulin administration schedules. Glycaemic control was improved on both insulin regimens, but was better on bedtime than morning insulin. Fasting plasma glucose (mmol l-1) was 12.0 +/- 0.7 (baseline), 8.6 +/- 0.7 (morning), and 4.6 +/- 0.3 (bedtime), respectively. Mean 24 h plasma glucose (mmol l-1) was 13.3 +/- 1.3, 9.0 +/- 0.7, and 7.8 +/- 0.7. Glycated haemoglobin (%) was 7.65 +/- 0.35, 6.23 +/- 0.26, and 5.81 +/- 0.32. The improvement of basal glycaemia is a consequence of increased basal metabolic clearance of glucose (baseline, 47.6 +/- 3.1 ml m-2 min-1; morning 63.5 +/- 5.4, bedtime 103.5 +/- 7.1). There was no change in hepatic glucose output. It is concluded that bedtime administration of intermediate acting insulin results in increased basal insulinaemia, leading to improved basal glycaemia and consequent improved overall metabolic control, compared to morning insulin administration. Therefore, bedtime may be the preferable timing of insulin therapy for patients with Type 2 diabetes and overt fasting hyperglycaemia.     

Control of non-insulin dependent diabetes is not correlated with endogenous insulin secretion

C-peptide was determined in seventy-one patients with non-insulin dependent diabetes mellitus (NIDDM) before and after a standard 500-calorie breakfast. Whereas in the normal-weight and obese controls the fasting C-peptide was 1.7-2.2 and postprandial maximum 6.0-6.6 ng/ml, in NIDDM the fasting level was only 2.4 +/- 1.5 ng/ml in spite of hyperglycemia of 234 mg/dl, and increased after breakfast to only 3.9 +/- 1.9 ng/ml. Fasting and postprandial levels of C-peptide correlated among themselves but did not correlate with age, duration of diabetes, body mass index, fasting or postprandial glycemia or--in the insulin-treated group--with the dose or duration of the treatment. There was no difference in glycemia between the subgroups of patients with the fasting C-peptide 5.9 +/- 1.7 and 1.0 +/- 0.2 ng/ml. No differences in any parameter were found between patients treated with insulin and with sulphonylureas.     

非胰岛素依赖型糖尿病病人心脏功能的改变

经静注潘生丁锝－９９ｍ标记的甲氧基异丁基异腈心肌断层显像术筛选后，用核素心室造影术评价非胰岛素依赖型糖尿病（ＮＩＤＤＭ）病人组１８例及对照组１６例在静息及极量运动状况下的心脏收缩功能变化；以多普勒超声心动图评价静息时心脏舒张功能改变。结果：静息状态下ＮＩＤ－ＤＭ组心率虽快于对照组，射血分数（ＥＦ）、峰射血率（ＰＥＲ）与对照组无差异；极量运动时则ＰＥＲ有统计学意义地明显低于对照组，且有４例ＥＦ较运动前降低＞５％，对照组无此现象，此差异接近显著意义（Ｐ＝０．０６５）．静息时ＮＩＤＤＭ组的Ｅ／Ａ比值降低，等容舒张时间延长，揭示ＮＩＤＤＭ病人心室收缩贮备功能降低，舒张功能在静息时已异常。     

Guar and gastric emptying in non-insulin dependent diabetes

Summary A gamma camera was used to measure gastric emptying in 10 non-insulin dependent diabetics and 10 control subjects during and after a breakfast meal of porridge labelled with^113mIn. In the diabetics there was a more rapid early phase and a more prolonged later phase of gastric emptying compared with controls. Incorporation of 10 g guar with the meal prolonged the later phase of gastric emptying in controls. However, guar did not significantly alter gastric emptying in the diabetics, although postprandial plasma glucose concentrations were reduced. The study demonstrates abnormalities of both the early and later phases of gastric emptying in an unselected group of non-insulin dependent diabetics. Guar reduced plasma glucose concentrations without affecting gastric emptying in these patients.     

Effect of insulin therapy on lipoproteins in non-insulin dependent diabetes mellitus (NIDDM)

Thirty patients with NIDDM and severe hyperglycemia (fasting plasma glucose greater than 200 mg/dl) were initiated on insulin therapy. Lipoprotein concentrations were measured by the Vertical Autoprofile procedure before insulin therapy and 1, 3, 6 and 26 weeks after insulin initiation. Patients were divided into 4 phenotypes based on their pretreatment lipoprotein profile: HyperVLDL (elevated VLDL), HyperLDL (elevated LDL), HyperVLDL-LDL (elevated VLDL and LDL), and non-hyperlipidemic. There were no differences in the initial fasting plasma glucose, Hgb Alc, or fasting free insulin concentrations between the groups. Both the HyperVLDL and HyperLDL groups had significantly lower HDL-C concentrations that the non-hyperlipidemic group and the HyperVLDL-LDL group had significantly higher IDL-C than any of the other groups. Insulin therapy resulted in similar decreases in fasting plasma glucose and increases in fasting free insulin concentrations in all 4 groups. HDL-C increased in all 4 groups. The most marked improvements in HDL-C were seen in the non-hyperlipidemic (+37%) and HyperLDL (+42%) groups while the HyperVLDL group had only an 18% increase. VLDL-C fell in all groups but in the HyperVLDL group it fell dramatically to almost normal levels within the first week, whereas it took 6 weeks for the HyperVLDL-LDL group to reach its VLDL-C nadir and this was still significantly higher than normal. LDL-C improved modestly in only the HyperLDL patients after 6 weeks of insulin therapy. There were no statistically significant changes in either the IDL-C or Lp(a)-C in any of the groups during insulin therapy. The changes in HDL-C and IDL-C were negatively correlated with the fasting plasma glucose and Hgb Alc but not with the free insulin concentration. We conclude that: 1) Insulin therapy can cause dramatic improvements in HDL-C and VLDL-C while it has only a mild suppressive effect on LDL-C and no statistically significant effect on IDL-C or Lp(a)-C. The degree of improvement in the lipid profiles varied considerably between the different lipid phenotypes. 2) The hyperlipidemic phenotypes seen in these patients appear to be determined primarily by factors other than the degree of hyperglycemia and hypoinsulinemia.     

Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in non-obese diabetic mice

The spontaneous development of insulin dependent diabetes mellitus in non-obese diabetic (NOD) mice has been shown to be mediated by a Th1 response against beta cell antigens. It is known that in murine models of Schistosoma mansoni infection, egg production is associated with a switch from a Th1 to Th2 response. This subsequent dominance of a Th2 response in S.mansoni infected mice has been shown to influence the response to other infectious agents or antigens. We therefore determined whether infection with S.mansoni could influence the spontaneous incidence of insulin dependent diabetes mellitus (IDDM) in NOD mice. Infection with this helminth significantly reduced the spontaneous incidence of IDDM. IDDM was also prevented by injecting parasite eggs alone. Because until relatively recently humans might expect to succumb to a variety of infectious agents, the current freedom from infection might permit the expression of a genetic predisposition to autoimmune pathology and be responsible for the increased incidence of IDDM.     

Silent myocardial ischaemia in patients with essential arterial hypertension and non-insulin dependent diabetes mellitus.

The concomitant presence of diabetes mellitus and arterial hypertension significantly impairs myocardial function through a direct negative effect on cardiac myocytes, coronary microvessels and precipitation of atherosclerosis in major coronary arteries. The purpose of the present study was to establish to what extent non-insulin dependent diabetes mellitus (NIDDM) modified silent myocardial ischaemia (SMI) in patients with essential hypertension and without documented coronary artery disease (CAD). The study population consisted of 41 patients with essential arterial hypertension associated with NIDDM, treated with diet and oral hypoglycaemic agents (group I) and 40 patients with essential arterial hypertension without diabetes mellitus (group II). Both groups were comparable with respect to age, gender, duration, severity and complications of hypertension. A mean duration of diabetes mellitus in group I was 6.8 years. Conventional and automatic blood pressure and heart rate measurements, continuous ECG recordings, echocardiograms and laboratory tests were obtained in all patients. SMI was more frequent in group I than in group II (29.3% vs 12.5%, P < 0.05). In group I the total duration of SMI was longer (37.3 vs 2.8 min, P < 0.001) and the total number of silent episodes was larger (15.5 vs 2.6, P < 0.001). No inter-group differences were seen in conventional and automatic blood pressure and heart rate measurements. Both groups did not differ significantly in left ventricular mass index (LVMI) or the proportion of patients with left ventricular hypertrophy (LVH) (75.6% vs 60%). Lipid profile in both groups indicated an increased risk of CAD, but without significant differences. In conclusion, in patients with essential arterial hypertension and diabetes mellitus, the incidence and severity of SMI were clearly higher than in hypertensives with normal carbohydrate metabolism. Employment of modern diagnostic techniques in hypertensives permits identification of those at greater risk, which may have further clinical implications.     

Effects of prolonged Acipimox treatment on glucose and lipid metabolism and on in vivo insulin sensitivity in patients with non-insulin dependent diabetes mellitus.

The effect of prolonged treatment with Acipimox on in vivo peripheral insulin sensitivity, and on glucose and lipid metabolism, was investigated in patients with NIDDM in a double-blind study. Twelve NIDDM patients were randomized to treatment with either placebo or Acipimox in pharmacological doses (250 mg x 3) for three months. Fasting plasma glucose, insulin, C-peptide and HbA1c concentrations were unaffected after three months of acipimox treatment. However, fasting plasma non-esterified fatty acid (NEFA) concentrations were twofold elevated after Acipimox treatment (1.34 +/- 0.09 vs 0.66 +/- 0.09 mmol/l; p < 0.05). Despite this, repeated acute Acipimox administration after the three months' treatment period enhanced total insulin-stimulated glucose disposal to the same extent as acute Acipimox administration before the treatment period (367 +/- 59 vs 392 +/- 66 mg.m-2.min-1, NS; both p < 0.05 vs placebo glucose disposal) (267 +/- 44 mg.m-2.min-1). In conclusion, insulin resistance or tachyphylaxis towards the effects of Acipimox on insulin stimulated glucose disposal was not induced during prolonged Acipimox treatment. The lack of improvement of blood glucose control in the patients with NIDDM may be due to the demonstrated rebound effect of lipolysis.     

Increase in left ventricular chamber stiffness in patients with non-insulin dependent diabetes mellitus

Indices of left ventricular ejection and diastolic filling were measured by cineventriculography in 11 patients with non-insulin dependent diabetes mellitus without significant coronary stenosis and 11 control subjects without diabetes mellitus. Indices of left ventricular ejection, such as ejection fraction and peak ejection rate, were the same in the two groups. The left ventricular end-diastolic volume index and the rapid filling volume index were significantly smaller, the peak filling rate was lower, the left ventricular end-diastolic pressure was higher and the modulus of left ventricular chamber stiffness was larger in the diabetic patients than in the control subjects. These results indicate that left ventricular chamber stiffness is increased in patients with non-insulin dependent diabetes mellitus.     

动态血压监测在非胰岛素依赖型糖尿病中的应用

对50例血压正常的非胰岛素依赖型糖尿病（NIDDM）患者进行24h动态血压监测（ABPM）。结果NIDDM组的24h平均舒张压（9．8±1．2kPa）、白天平均舒张压（10．0±1．2kPa）、夜间平均舒张压（9．5±1．2kPa）均比对照组（分别为8．8±1．0、9．1±1．0、8．1±1．1kPa）明显升高，夜间收缩压及舒张压下降百分率均明显降低，昼夜节律消失。有糖尿病肾病组患者眼底视网膜病变发生率高。提示随着血压昼夜节律的消失及夜间血压持续升高，可能导致肾病变及视网膜血管病变的发生。     

Metformin increases insulin sensitivity and basal glucose clearance in Type 2 (non-insulin dependent) diabetes mellitus

Abstract The effects of metformin on glycaemia, insulin and c-peptide levels, hepatic glucose production and insulin sensitivity (using the euglycaemic, hyperinsulinaemic clamp) were evaluated at fortnightly intervals in 9 Type 2 diabetic patients using a stepwise dosing protocol: Stage 1 - no metformin for four weeks; stage 2 - metformin 500mg mane; stage 3 - metformin 500mg thrice daily; stage 4 – metformin 1000mg thrice daily. Results are expressed as Mean ± SEM. Fasting blood glucose decreased from basal values (9.7 ±1.0 mmol/L) by 13% at stage 2, 34% at stage 3 and 41% at stage 4 (p<0.02 vs basal for all stages; p<0.02 stage 2 vs stage 3). Post-prandial glycaemia was significantly improved only with metformin 3000mg/day (p<0.05). Fasting, meal-stimulated and total insulin and c-peptide levels showed no change. Hepatic glucose output did not change significantly with metformin. Insulin sensitivity, measured as total glucose utilisation during hyperinsulinaemia, increased from stage 1 (10.3 ± 2.1 μmoL/kg/min) by 23% at stage 3 (p < 0.05) and by 29% at stage 4 (p < 0.02). Basal metabolic clearance of glucose increased compared to stage 1 (1.69 ±0.16 mL/kg/min) by 30% at stage 2, 53% at stage 3 and 44% at stage 4 (all p <0.02). This study demonstrates that improved efficiency of glucose utilisation, both basally and under conditions of euglycaemic hyperinsulinaemia, is the basis of metformin's antihyperglycaemic action.     

Assessment of plasma lipid profile oxysterols and vitamin E concentration in morbidity obese patients with coexisting arterial hypertension and non-insulin dependent diabetes mellitus

Morbid obesity (BMI > or = 40 kg/m2) is accompanied by lipid disturbances which may be involved in the increased incidence of arterial hypertension and non-insulin dependent diabetes mellitus. The aim of the study was to assess plasma concentrations of total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides (TG) and two parameters of oxidation stress--vitamin E and oxysterols, in morbidly obese patients with coexisting arterial hypertension and non-insulin dependent diabetes mellitus. Studies were performed in 37 morbidly obese patients divided into three groups: group I--without coexisting diseases, group II--with arterial hypertension, and group III--with arterial hypertension and non-insulin dependent diabetes mellitus. In all groups there was an increase in TG concentration, a decrease in HDL-cholesterol level, and normal values of TC and LDL-cholesterol. The concentrations of 7-hydroxycholesterols (7-OH) in group II (602.65 +/- 264.46 ng/ml) and group III (570.94 +/- 210.59 ng/ml) were significantly higher compared to that in group I (336.09 +/- 220.74 ng/ml). There were no differences between groups in concentrations of 7-ketocholesterols (7-K), TC, HDL-cholesterol, LDL-cholesterol, TG, vitamin E and vitamin E/(TC + TG) ratio. In all groups TC concentration correlated positively with TG concentration, and negatively with vitamin E/(TC + TG) ratio. Moreover, the positive correlation between TG and HDL-cholesterol concentrations, and negative correlation between plasma vitamin E and 7-K concentrations were demonstrated. In conclusion, although the study demonstrates similar disturbances in lipid profile and oxidation stress parameters in all groups, with significant differences in 7-OH only, the role of cholesterol oxidation products in pathogenesis of arterial hypertension and non-insulin dependent diabetes mellitus in morbidly obese patients cannot be excluded.