Hypertriglyceridemia in different degrees of glucose intolerance in a Finnish population-based study.

OBJECTIVE--To determine the prevalence of hypertriglyceridemia and the mean serum triglyceride concentrations in different degrees of glucose tolerance--non-insulin-dependent diabetes mellitus (NIDDM), impaired glucose tolerance (IGT), and normal glucose tolerance (NGT). In addition, we analyzed the correlates of serum triglyceride concentration to explain why it is more prevalent in diabetic subjects. RESEARCH DESIGN AND METHODS--This study was a cross-sectional survey of 4000 people aged 45-64 yr randomly drawn from the population register of the Finnish population of the provinces of North Karelia and Kuopio in eastern Finland and Turku/Loimaa area in southwestern Finland and stratified by four 10-yr age- and sex groups. The final material comprised 96 subjects with NIDDM, 102 subjects with IGT, and 323 subjects with normal glucose tolerance classified on the basis of two 2-h oral glucose tolerance tests. The prevalence of hypertriglyceridemia by the glucose tolerance status and the variation in serum triglycerides associated with selected life-style and biochemical factors were executed as the main outcome measures. RESULTS--The prevalence of hypertriglyceridemia (greater than or equal to 2.3 mM) was 47.6% (95% confidence interval [CI] 32.5-62.7%) in NIDDM men, 21.9% (95% CI 7.6-36.2%) in IGT men, and 15.4% (95% CI 9.3-21.5%) in NGT. In women, hypertriglyceridemia was found in 51.9% (95% CI 38.6-65.2%) among those with NIDDM, 25.7% (95% CI 15.5-35.9%) among those with IGT, and 10.7% (95% CI 6.3-15.1%) in women with NGT. After adjusting for body mass index (BMI) and age, the difference in the prevalence of hypertriglyceridemia between the glucose tolerance groups remained significant in both men (P = 0.008) and women (P = 0.0001). High serum total cholesterol, high BMI, high waist-hip ratio, and low high-density lipoprotein (HDL) cholesterol were significantly associated with high serum triglycerides in all glucose tolerance groups. No synergistic effect between these parameters and glucose tolerance status was found. In multiple linear regression analyses, fasting plasma insulin, diabetes status, and serum uric acid were significant predictors of serum triglyceride concentration after taking into account age, BMI, and HDL and total cholesterol. The association between BMI and serum triglycerides in the regression analysis was significant only when plasma insulin was not included in the model. CONCLUSIONS--Hypertriglyceridemia is common in subjects with NIDDM and IGT and is often associated with low HDL cholesterol, high total cholesterol, hyperinsulinemia, and elevated serum uric acid concentration.     

家族性2型糖尿病遗传方式及血糖血脂代谢的研究

目的 :探索家族性 2型糖尿病的遗传方式及家族性 2型糖尿病家系一级亲属正常糖耐量同胞的血糖血脂代谢变化。方法 :按WHO1980标准 ,收集江苏苏南地区 2型糖尿病多发家系 99个 ,进行 3代家族史和血统成员的调查研究。检查血糖、血脂、葡萄糖耐量及胰岛素C肽释放试验。在排除糖尿病和糖耐量减低 (IGT)的前提下 ,选择先证者的正常糖耐量同胞为观察组 (5 4例 ) ,同胞的正常配偶为对照组 (5 6例 ) ,进行血糖血脂代谢分析。结果 :先证者的同胞患病率为 46 7%。同胞患病率是其配偶的 6.6倍 ;而同胞及其配偶的IGT患病率均为 11%左右。病系谱分析显示 ,至少双亲之一为糖尿病患者的家系达5 0 .5 % ,先证者同胞患糖尿病者达 1/ 2。与配偶组比较同胞的TG、LDL水平升高 ,空腹血糖升高 ,而胰岛素、C肽水平无差异。结论 :有家族史的 2型糖尿病患者有明显的家族聚集性 ,其发病与遗传密切相关 ,其遗传方式不完全支持多基因遗传 ,而支持孟德尔的常染色体显性遗传。同胞在糖耐量正常的情况下血糖、血脂已开始变化 ,对该糖尿病高危人群应进行血糖血脂监测以利早期防治。     

Prevalence of diabetes and impaired glucose tolerance in elderly subjects and their association with obesity and family history of diabetes

The goal of this study was to investigate the prevalence of impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) in elderly subjects and their association with obesity, central obesity, and a family history of diabetes. A representative population sample of 1300 subjects (471 men, 829 women) aged 65-74 yr participated in the study. The participation rate was 71%. The prevalence rates of previously and newly diagnosed NIDDM and IGT, based on a history of diabetes and an oral glucose tolerance test, were 8.7, 7.0, and 17.8% in men and 11.7, 7.1, and 19.1% in women. Thus, 33.8% of men and 37.9% of women had abnormal glucose tolerance according to World Health Organization criteria. Obesity (body mass index greater than or equal to 27 kg/m2 in men and greater than or equal to 25 kg/m2 in women) and central obesity (waist-hip ratio greater than or equal to 0.98 in men and greater than or equal to 0.89 in women) doubled the prevalence of IGT or NIDDM. The combination of obesity and a family history of diabetes was associated with a more marked increase in the prevalence of IGT or NIDDM in men than in women. Simultaneous presence of obesity, central obesity, and a family history of diabetes was associated with a threefold increase in the prevalence of IGT or NIDDM (65.4 vs. 24.1% in men, 52.8 vs. 19.6% in women, P less than 0.001). The major risk factors for NIDDM, e.g., obesity, central fat distribution, and a family history of diabetes, explained 10% of the variance in 2-h glucose values in multiple regression analysis. In conclusion, the prevalence of IGT and NIDDM was high in elderly subjects. Although obesity, central fat distribution, and a family history of diabetes were significantly associated with the increased prevalence of IGT or NIDDM, they explained only a minor proportion of the variance in 2-h glucose values.     

High blood pressure and insulin resistance: influence of ethnic background

Hyperinsulinaemia links non-insulin dependent diabetes (NIDDM), obesity, and hypertension, each an insulin-resistant state in its own right. Insulin resistance predicts the occurrence of NIDDM, and plays a major role in its pathogenesis. We tested the hypothesis that hyperinsulinaemia may also predict hypertension in a sample (n = 2905) of the mixed population of San Antonio, in which hyperinsulinaemia and NIDDM are more prevalent among Mexican-Americans than non-Hispanic whites. Whilst in the whole sample the hypertensives had significantly (P less than 0.001) higher plasma insulin concentrations than the normotensives, high blood pressure was significantly (P less than 0.01) more frequent among non-Hispanic whites than Mexican-Americans regardless of diabetes status. After adjusting for factors (age, sex, body mass, and body fat distribution) known to affect insulin levels, a direct relationship between post-glucose plasma insulin concentrations and prevalence of hypertension was still present in both ethnic groups. In Mexican-Americans, however, the standardized prevalence of hypertension was significantly (P less than 0.001) lower at any given insulin concentration. Post-glucose plasma glucose levels also were directly related to hypertension prevalence in both groups; again, the regression line was shifted downward and, furthermore, less steep (P less than 0.02) in Mexican-Americans, suggesting relative protection against the negative effect of hyperglycaemia on blood pressure. Dyslipidaemia (higher total cholesterol and triglyceride, and lower HDL-cholesterol concentrations) was strongly associated with hyperinsulinaemia and blood pressure in both ethnic groups. After adjusting for plasma insulin, only hypertriglyceridaemia was associated with high blood pressure, with no inter-ethnic difference.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cholesterol guidelines, lipoprotein cholesterol levels, and triglyceride levels: potential for misclassification of coronary heart disease risk

By using National Cholesterol Education Program guidelines for serum cholesterol (less than 200 mg/dl is designated "desirable," and 200 to 239 mg/dl is designated "borderline-high," and greater than or equal to 240 mg/dl is designated "high"), low-density and high-density lipoprotein (LDL, HDL) cholesterol levels and triglyceride levels were quantitated in 897 self-referred fasting subjects to assess the potential for coronary risk misclassification. With cholesterol less than 200 mg/dl, misclassification was arbitrarily identified by an LDL level greater than or equal to the 75th percentile, a triglyceride level greater than or equal to the 90th percentile, or an HDL level less than or equal to the 10th percentile. With the cholesterol level in the 200 to 239 mg/dl range, misclassification was identified by an LDL level greater than or equal to the 75th percentile, a triglyceride level greater than or equal to the 90th percentile, and an HDL level less than or equal to the 10th percentile or greater than or equal to the 90th percentile (or both). With a cholesterol level greater than or equal to 240 mg/dl, misclassification was identified by an HDL level less than or equal to the 10th percentile, or greater than or equal to the 90th percentile. With the cholesterol level less than 200 mg/dl, misclassification is rare, occurring in 14.5% of the subjects. With the cholesterol level in the 200 to 239 mg/dl range, and greater than or equal to 240 mg/dl, misclassification occurred in 46.7% and 17.6% of the subjects, respectively. The importance of routine lipoprotein analysis when the cholesterol level is greater than or equal to 240 mg/dl is emphasized by the finding that 65% of the subjects in this category had top quartile LDL levels, 8% had bottom decile HDL levels, and 30% had top decile triglyceride levels. To avoid misclassification, fasting HDL, LDL, and triglyceride levels should probably be measured in all subjects with screening cholesterol levels greater than or equal to 200. There is remarkably little misclassification with top quartile LDL or bottom decile HDL levels (or both) when the cholesterol level is less than 200 mg/dl.     

Insulin resistance and insulin secretory dysfunction are independent predictors of worsening of glucose tolerance during each stage of type 2 diabetes development

OBJECTIVE: Although prospective studies indicate that insulin resistance and insulin secretory dysfunction predict type 2 diabetes, they provide limited information on the relative contributions of both abnormalities to worsening glucose tolerance at different developmental stages of the disease. We therefore assessed the predictive effect of insulin resistance and insulin secretory dysfunction separately for the progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) and from IGT to diabetes. RESEARCH DESIGN AND METHODS: Insulin-stimulated glucose disposal (M) (hyperinsulinemic clamp), acute insulin secretory response (AIR) (25-g intravenous glucose tolerance test), and body composition (hydrodensitometry or dual-energy X-ray absorptiometry) were measured in 254 Pima Indians with NGT and in 145 Pima Indians with IGT, who were then followed for 0.5-13 years. RESULTS: After follow-ups of 4.4 +/- 3.1 and 5.5 +/- 3.4 years, 79 (31%) of the subjects with initial NGT had developed IGT, and 64 (44%) of the subjects with initial IGT had developed diabetes. In proportional-hazards analyses with adjustment for age, sex, and percent body fat, low M and low AIR were independent predictors of both the progression from NGT to IGT (relative hazards [95% CI] for 10th vs. 90th percentile: M 2.4 [1.2-4.7], P < 0.02; AIR 2.1 [1.1-4.1], P < 0.04) and from IGT to diabetes (M 2.5 [1.3-5.0], P < 0.01; AIR 1.8 [0.99-3.3], P = 0.055). CONCLUSIONS: During each stage of the development of type 2 diabetes, insulin resistance and insulin secretory dysfunction are independent predictors of worsening glucose tolerance and are, therefore, both targets for the primary prevention of the disease.     

Insulin antibodies in non-insulin-dependent diabetes mellitus: effect of treatment with semisynthetic human insulin

This multicenter study of patients with non-insulin-dependent diabetes mellitus (NIDDM) was undertaken (1) to determine the incidence of insulin antibody formation in such patients before exposure to exogenous insulin; (2) to assess the long-term immunologic response to semisynthetic human insulin (ssHI) in new insulin users and in patients transferred from animal insulin; and (3) to document the efficacy and safety of ssHI in both new and transfer patients. In addition, a substudy at one participating center was designed to compare the effects of a twice-daily versus a once-daily regimen in initiating ssHI therapy in new patients with uncontrolled NIDDM. Among the 37 new patients, only one had detectable insulin antibody levels before administration of insulin. After ssHI therapy was begun, this patient's antibody levels rapidly fell below the assay's limit of detection. Detectable levels of antibodies to human insulin were found in only 36% of 28 new patients after 12 months of therapy. As expected, the prevalence of insulin antibodies among animal-insulin users was high: 82% of the 17 transfer patients had detectable insulin antibody levels (mean, 2.27 mU/ml) at baseline. After six months of treatment with ssHI, antibody levels decreased significantly (mean, 0.75 mU/ml; P less than 0.05). Control of glycemia was assessed by measurement of glycosylated hemoglobin. Values decreased significantly (P less than 0.01) in the new patients after the introduction of ssHI and remained stable in the transfer group after initiation of ssHI therapy. Hypoglycemic episodes were infrequent in both groups. In initiating ssHI therapy in new patients hospitalized with uncontrolled NIDDM, a twice-daily regimen resulted in a more rapid normalization of glycemia and earlier discharge than did the standard once-daily regimen. In conclusion, the results of this study provide further evidence that NIDDM and insulin-dependent diabetes mellitus (IDDM) are immunologically different disorders, with the immune system probably not involved in the pathogenesis of NIDDM. The data also indicate that ssHI is less immunogenic than animal insulin and that it is effective and safe in the management of NIDDM both in first-time insulin users and in patients transferred from animal-species insulin. Thus ssHI would appear to be useful in treating NIDDM, especially in patients who require intermittent insulin therapy.     

Prevalence of insulin deficiency among initially non-insulin-dependent middle-aged diabetic individuals

The endogenous insulin secretion capacity of 171 insulin-treated middle-aged persons with diabetes (81 men, 90 women) of the Kuopio University Central Hospital district (population 250,000), East Finland, was measured by the C-peptide response to glucagon. The prevalence of insulin deficiency among initially non-insulin-dependent diabetic (NIDDM) individuals was calculated on the basis of those who were initially treated with diet or oral drugs and 3 yr or more after diagnosis had been treated with insulin and were insulin deficient in this study. The prevalence of complete insulin deficiency (postglucagon C-peptide undetectable) was among initially NIDDM individuals of the same region, 0.7% in men and 1.2% in women. Using the postglucagon C-peptide level of 0.20 nmol/L as a cut-off point, the prevalence of insulin deficiency was 2.0% in men and 1.9% in women and, on the basis of C-peptide level of 0.60 nmol/L, the prevalence of insulin deficiency was 3.5% in men and 2.7% in women. Our data suggest that the deterioration of insulin secretion capacity in NIDDM to the level that leads to insulin dependency occurs less often than has been previously suggested.     

Multiple defects in muscle glycogen synthase activity contribute to reduced glycogen synthesis in non-insulin dependent diabetes mellitus.

To define the mechanisms of impaired muscle glycogen synthase and reduced glycogen formation in non-insulin dependent diabetes mellitus (NIDDM), glycogen synthase activity was kinetically analyzed during the basal state and three glucose clamp studies (insulin approximately equal to 300, 700, and 33,400 pmol/liter) in eight matched nonobese NIDDM and eight control subjects. Muscle glycogen content was measured in the basal state and following clamps at insulin levels of 33,400 pmol/liter. NIDDM subjects had glucose uptake matched to controls in each clamp by raising serum glucose to 15-20 mmol/liter. The insulin concentration required to half-maximally activate glycogen synthase (ED50) was approximately fourfold greater for NIDDM than control subjects (1,004 +/- 264 vs. 257 +/- 110 pmol/liter, P less than 0.02) but the maximal insulin effect was similar. Total glycogen synthase activity was reduced approximately 38% and glycogen content was approximately 30% lower in NIDDM. A positive correlation was present between glycogen content and glycogen synthase activity (r = 0.51, P less than 0.01). In summary, defects in muscle glycogen synthase activity and reduced glycogen content are present in NIDDM. NIDDM subjects also have less total glycogen synthase activity consistent with reduced functional mass of the enzyme. These findings and the correlation between glycogen synthase activity and glycogen content support the theory that multiple defects in glycogen synthase activity combine to cause reduced glycogen formation in NIDDM.     

High systolic blood pressure increases prevalence and severity of retinopathy in NIDDM patients.

OBJECTIVE--To determine whether the severity of retinopathy is higher in a group of NIDDM patients with sBP greater than or equal to 140 mmHg compared with NIDDM patients with sBP less than 140 mmHg. RESEARCH DESIGN AND METHODS--Ophthalmoscopy and FAG were conducted among a group of NIDDM patients with either a sBP above (n = 54) or below (n = 55) 140 mmHg. The groups were matched according to diabetes duration, metabolic control (HbA1c), and AER. RESULTS--Patients with sBP greater than 140 mmHg had a higher prevalence of retinopathy, as established according to a rating scale (4.9 +/- 3.8 vs. 3.2 +/- 3.3, P less than 0.02); furthermore, their BMI values were higher (28.1 +/- 4.5 vs. 24.9 +/- 4.1 kg/m2, P less than 0.001). The group of normotensive subjects showed the highest rate of low grading (0-2) values. However, the highest prevalence rates of 8-10 grading values (proliferative retinopathy) were found in the hypertensive group. CONCLUSIONS--These data suggest that sBP values greater than or equal to 140 mmHg favor the onset of retinopathy in NIDDM patients during their 1st 10 yr of disease.     

Low frequency of 5'-flanking insertion of human insulin gene in Japanese non-insulin-dependent diabetic subjects

Polymorphism in the 5'-flanking region of the human insulin gene in 149 unrelated Japanese subjects [77 with non-insulin-dependent diabetes mellitus (NIDDM), 17 with insulin-dependent diabetes mellitus (IDDM), and 55 controls] was analyzed with Southern blot hybridization. We used the size of the hybridized fragments to classify the locus into three groups according to Bell's method (a short, class 1 allele averaging 570 base pairs; an intermediate-size, class 2 allele averaging 1320 base pairs, and a long, class 3 allele averaging 2470 base pairs in size). The allelic frequency of classes 2 and 3 in 298 alleles was 5.0% and in the 146 alleles of NIDDM, 7.8%. The value is lower than in Caucasians, American Blacks, and Pima Indians, and the results suggest that the 5'-flanking insertion is not a genetic marker in most NIDDM patients who are Japanese. However, the frequency of the 5'-flanking insertion in those who were not obese and had a family history of diabetes was higher than that of other NIDDM patients (P = .013), and the frequency in NIDDM patients with onset of diabetes at age less than or equal to 39 yr was lower than those whose onset was at age greater than or equal to 40 yr (P = .053). As NIDDM is a heterogeneous disorder, further analysis is needed. These results suggest that we cannot completely exclude the meaning of the insertion in NIDDM. On the other hand, the frequency in IDDM was 0%, lower than in NIDDM (P = .094). Because the number of subjects studied was small, this result is speculative.     

Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus.

The increased prevalence of non-insulin-dependent diabetes mellitus (NIDDM) among women with polycystic ovary syndrome (PCOS) has been ascribed to the insulin resistance characteristic of PCOS. This study was undertaken to determine the role of defects in insulin secretion as well as familial factors to the predisposition to NIDDM seen in PCOS. We studied three groups of women: PCOS with a family history of NIDDM (PCOS FHx POS; n = 11), PCOS without a family history of NIDDM (PCOS FHx NEG; n = 13), and women without PCOS who have a family history of NIDDM (NON-PCOS FHx POS; n = 8). Beta cell function was evaluated during a frequently sampled intravenous glucose tolerance test, by a low dose graded glucose infusion, and by the ability of the beta cell to be entrained by an oscillatory glucose infusion. PCOS FHx POS women were significantly less likely to demonstrate appropriate beta cell compensation for the degree of insulin resistance. The ability of the beta cell to entrain, as judged by the spectral power for insulin secretion rate, was significantly reduced in PCOS FHx POS subjects. In conclusion, a history of NIDDM in a first-degree relative appears to define a subset of PCOS subjects with a greater prevalence of insulin secretory defects. The risk of developing NIDDM imparted by insulin resistance in PCOS may be enhanced by these defects in insulin secretion.     

Improvement of insulin-induced glucose disposal in obese patients with NIDDM after 1-wk treatment with d-fenfluramine

OBJECTIVE: To study the short-term effects of the serotoninergic anorectic drug d-fenfluramine on insulin-induced glucose disposal. RESEARCH DESIGN AND METHODS: A randomized double-blind placebo-controlled crossover trial with 1-wk treatment periods (2 x 15 mg/day d-fenfluramine) was conducted. Twenty obese subjects, 10 with normal oral glucose tolerance and 10 with non-insulin-dependent diabetes mellitus (NIDDM), were all treated with a weight-maintaining diet. Euglycemic-hyperinsulinemic glucose clamps with measurement of glucose kinetics with D-[3-3H]glucose were performed at either two (patients without NIDDM, 0.05 and 0.10 U.kg-1.h-1) or three (patients with NIDDM, 0.05, 0.10, and 0.50 U.kg-1.h-1) insulin delivery rates. RESULTS: In the nondiabetic subjects, no significant changes in any metabolic or hormonal parameter were measured in the basal state or during the clamp despite a slight reduction in body weight (-1.2 +/- 0.5 kg, P less than 0.05). In the diabetic patients, no significant changes in body weight or basal plasma insulin levels were observed, but fasting blood glucose levels (8.0 +/- 0.8 vs. 9.4 +/- 1.1 mM, P less than 0.005) and plasma free fatty acid concentrations (1150 +/- 227 vs. 1640 +/- 184 microM, P less than 0.05) were significantly reduced after d-fenfluramine compared with placebo. During the clamp, insulin metabolic clearance rate (MCR) was similar after both placebo and d-fenfluramine; endogenous (hepatic) glucose production was similarly and almost completely suppressed, whereas glucose disposal was remarkably enhanced after d-fenfluramine (average increase of glucose MCR 35 +/- 12%, P less than 0.02). CONCLUSIONS: Whatever the mechanism(s) involved, a 1-wk treatment with d-fenfluramine induces better blood glucose control and improves insulin sensitivity in obese patients with NIDDM independent of significant weight reduction; this last effect is not present in obese subjects with normal oral glucose tolerance.     

Intracellular glucose oxidation and glycogen synthase activity are reduced in non-insulin-dependent (type II) diabetes independent of impaired glucose uptake.

To examine whether reduced rates of oxidative (Gox) and non-oxidative (Nox) glucose metabolism in non-insulin-dependent diabetes mellitus (NIDDM) are due to reduced glucose uptake, intrinsic defects in intracellular glucose metabolism or increased fat oxidation (Fox), indirect calorimetry was performed at similar glucose uptake rates in eight nonobese NIDDM and eight comparable nondiabetic subjects. Three glucose clamp studies were performed: one in the nondiabetic and two in the NIDDM subjects. In the nondiabetic subjects, glucose uptake was increased to 7.62 +/- 0.62 mg/kg of fat-free mass (FFM) per min by increasing serum insulin to 309 pmol/liter at a glucose concentration of 5.1 mmol/liter. By raising the concentration of either serum glucose or insulin fourfold in the NIDDM subjects, glucose uptake was matched to nondiabetic subjects (8.62 +/- 0.49 and 8.59 +/- 0.51 mg/kg FFM per min, respectively, P = NS). Skeletal muscle glycogen synthase activity and plasma lactate levels were measured to characterize Nox. When glucose uptake was matched to nondiabetics by hyperglycemia or hyperinsulinemia, Gox was reduced by 26-28% in NIDDM (P less than 0.025) whereas Fox was similar. Nox was greater in NIDDM (P less than 0.01) and was accompanied by increases in circulating lactate levels. Glycogen synthase activity was reduced by 41% (P less than 0.025) when glucose uptake was matched by hyperglycemia. Glycogen synthase activity was normalized in NIDDM, however, when glucose uptake was matched by hyperinsulinemia. Therefore, a defect in Gox exists in nonobese NIDDM subjects which cannot be overcome by increasing glucose uptake or insulin. Since both glucose uptake and Fox were similar in the two subject groups these factors were not responsible for reduced Gox. Increased Nox in NIDDM is primarily into lactate. Reduced glycogen synthase activity in NIDDM is independent of glucose uptake but can be overcome by increasing the insulin concentration.     

Patterns of glucose and lipid abnormalities in black NIDDM subjects.

OBJECTIVE: We had previously shown two variants among black non-insulin-dependent diabetic (NIDDM) subjects in a normoglycemic remission: one with insulin resistance and the other with normal insulin sensitivity. This study examined whether these two variants exist in the ordinary hyperglycemic black NIDDM population. Research Design and Methods: Fifty-two black NIDDM subjects were assessed for insulin-stimulated glucose disposal (euglycemic clamp), glycemic control (fasting plasma glucose and HbA1c), and fasting lipid profiles. RESULTS: The distribution of glucose disposal in 30 black NIDDM subjects (body mass index; BMI less than 30 kg/m2) was bimodal, which indicated two populations. Eighteen of 30 subjects (BMI 26.4 +/- 0.5 kg/m2) had insulin resistance (glucose disposal 3.21 +/- 0.24 mg.kg-1.min-1). Twelve of 30 subjects (BMI 24.83 +/- 1.1 kg/m2) had normal insulin sensitivity (glucose disposal 7.19 +/- 0.46 mg.kg-1.min-1). Twenty-one of the remaining 22 subjects (BMI 33.4 +/- 0.7 kg/m2) were insulin resistant (glucose disposal 2.88 +/- 0.21 mg.kg-1.min-1). Fasting serum triglyceride levels were lowest in the insulin-sensitive population (0.91 +/- 0.07 mM) and different from the insulin-resistant population, BMI less than 30 and greater than 30 kg/m2, (1.20 +/- 0.10 mM, P less than 0.05 and 1.42 +/- 0.17 mM, P less than 0.025, respectively). Fasting serum low-density lipoprotein cholesterol levels were not significantly different among the groups, although it did increase with insulin resistance and increasing obesity. Total serum cholesterol levels and glycemic control were similar for all three groups. Serum high-density lipoprotein cholesterol levels were higher in women compared with men. CONCLUSIONS: In the hyperglycemic black NIDDM population, two variants exist: one with insulin resistance and one with normal insulin sensitivity. This insulin-sensitive variant represents 40% of subjects with a BMI less than 30 kg/m2. Moreover, the insulin-sensitive group has a lower risk profile for cardiovascular disease.     

Prevalence and mortality of acute myocardial infarction in patients with diabetes

The purpose of this study was to investigate if insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) predispose to the development of acute myocardial infarction (AMI) and modify the prognosis. The study includes 832 AMI patients consecutively hospitalized over a 3-yr period. The prevalence of diabetes mellitus among the AMI patients was 9.7% and is significantly higher than in an age-matched population, where it is 6.1% (P less than 0.001). The prevalence of diabetes was higher for women than for men (14.9% versus 7.6%). The risk of AMI was found to be twice as high among IDDM than among nondiabetic patients (P less than 0.001). Men with NIDDM were not found to have a significantly higher risk of AMI (P greater than 0.1), but the risk of AMI in women with NIDDM was approximately doubled (P less than 0.01). During the first month following AMI the mortality rate for nondiabetic patients was 20.2% compared with 42.0% for diabetic patients (P less than 0.001). Insulin treatment in NIDDM was associated with a reduced mortality rate compared with treatment with oral agents (P less than 0.05). The mortality rate was significantly higher in patients with poor metabolic control compared with patients in good control, whether before AMI or at the time of hospitalization. Diabetic patients had a higher risk of developing cardiogenic shock and conduction disorders than nondiabetic patients. We conclude that diabetes mellitus disposes to AMI and that the mortality rate of AMI is significantly increased among diabetic patients. Poor metabolic regulation of the diabetes may aggravate the prognosis for AMI.     

Adipocyte insulin binding and action in moderately obese NIDDM patients after dietary control of plasma glucose: reversal of postbinding abnormalities

Studies of fat cells from patients with newly diagnosed, untreated non-insulin-dependent diabetes mellitus (NIDDM) have revealed severe abnormalities in insulin action on glucose transport and metabolism. To determine whether these defects can be reversed if good glycemic control is reached by dietary treatment, eight moderately obese NIDDM subjects were studied at diagnosis and again when the patients had been in good glycemic control induced by low-energy dieting for at least 2 mo (absence of glycosuria and fasting plasma glucose less than 7 mM). Average body weight decreased by 8 kg (P less than .05). Fasting plasma glucose decreased from 11.5 +/- 1.2 to 6.9 +/- 0.9 mM, whereas fasting serum insulin concentrations were unchanged. Adipocyte insulin binding at tracer concentration (15 pM, 37 degrees C) was not changed significantly (1.94 +/- 0.52 to 2.05 +/- 0.62% per 30 cm2 surface area/ml). The basal (non-insulin-stimulated) glucose transport (tracer glucose concentration 5 microM) increased from 25 +/- 12 to 44 +/- 14 pmol X 90 min-1 X 10 cm-2 surface area (P less than .02). The maximally insulin-stimulated glucose transport rate increased from 35 +/- 20 to 78 +/- 26 pmol/90 min (P less than .01). The percentage insulin response above basal levels increased from 31 +/- 40 to 89 +/- 58% (P less than .01). The insulin sensitivity (half-maximally stimulating insulin concentrations) was also improved (P less than .05). Glucose conversion rates to total lipids increased 34 +/- 62 and 65 +/- 80% in basal cells and maximally insulin-stimulated cells, respectively (.2 greater than P greater than .1, .1 greater than P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Inflammation and changes in metabolic syndrome abnormalities in US adolescents: findings from the 1988-1994 and 1999-2000 National Health and Nutrition Examination Surveys

BACKGROUND: Understanding of C-reactive protein (CRP) in adult metabolic syndrome is increasing; however, this relationship in children is less clear. METHODS: We compared the prevalence of metabolic abnormalities and metabolic syndrome in fasting 12- to 19-year-olds from the 1999-2000 and 1988-1994 National Health and Nutrition Examination Survey (NHANES). In the more recent dataset we explored the relationship between metabolic abnormalities and CRP as measured by a high-sensitivity assay. RESULTS: The prevalence of central obesity, low HDL-cholesterol, and hypertension increased between the 2 surveys. Three or more abnormalities (metabolic syndrome) were found in 12.7% [95% confidence interval (CI), 10.0%-15.4%] of fasting adolescents from the 1999-2000 survey, compared with 9.2% (95% CI, 7.8%-10.6%; P < 0.001) in the 1988-1994 dataset, with increases also seen in sex and ethnic/racial subgroups. Increases in metabolic syndrome were primarily attributable to increasing body mass index (BMI); prevalence of BMI at or above the 85th percentile increased from 25.9% to 30.5%. Metabolic syndrome was much more prevalent in overweight compared with normal-weight adolescents (38.6% vs 1.4%; P < 0.001). Median CRP increased with increasing numbers of metabolic abnormalities and was higher in adolescents with metabolic syndrome than in those without. CRP was higher in adolescents with BMI at or above the 85th percentile than those with normal BMI. CONCLUSIONS: Metabolic abnormalities and the metabolic syndrome phenotype are increasingly prevalent in US adolescents, attributable in part to the increasing incidence of overweight. Adolescents with more metabolic abnormalities have higher CRP, which may be an indicator of greater metabolic derangement and future cardiovascular risk.     

Treatment of NIDDM with insulin agonists or substitutes

Non-insulin-dependent diabetes mellitus (NIDDM) is a common disorder occurring in 3-6% of adults in most western populations. In the United States, 29% of patients with diabetes take insulin; of these, 76% have NIDDM. Insulin therapy is usually required at some time in NIDDM. Insulin therapy improves the abnormalities of NIDDM (reduced beta-cell function, increased hepatic glucose production, reduced peripheral glucose disposal, lipid abnormalities). Insulin and sulfonylurea agents have comparable effects on mild forms of NIDDM, but for more severe forms, insulin is usually superior. Combination insulin-sulfonylurea treatment may improve the response to sulfonylureas, although long-term well-controlled trials have not been conducted. Short-term insulin treatment may restore response to sulfonylureas. Other promising treatments (human proinsulin, nasal insulin, somatostatin) have not shown any advantage over conventional insulin therapy. Insulin causes hypoglycemia and peripheral hyperinsulinemia. The hazards of hyperinsulinemia, e.g., weight gain and hypoglycemia, have been overstated, and questions about its atherogenic effects remain to be resolved. The effect of glycemic control on macro- and microvascular complications has not been established; however, maintaining fasting blood glucose levels of less than 6.7 mM may protect against progression of retinopathy, neuropathy, and nephropathy and reduce the severity of ischemic stroke. Dosage algorithms generally use intermediate- or long-acting insulin to control basal glycemia, with regular insulin added before meals if needed to control postprandial glycemia. Effective therapy depends on the patient being informed, cooperative, and willing to self-monitor blood glucose. Insulin treatment intermittency increases the risk for immune complications (resistance and allergy). Overall, patients with NIDDM can benefit from insulin therapy.     

Improvement in in vitro insulin action after one month of insulin therapy in obese noninsulin-dependent diabetics. Measurements of glucose transport and metabolism, insulin binding, and lipolysis in isolated adipocytes

It has been previously reported that maximum insulin-stimulated glucose transport and utilization were both decreased, while basal lipolysis was increased in adipocytes from obese subjects with noninsulin-dependent diabetes mellitus (NIDDM). To determine whether these values can be returned towards those obtained in equally obese subjects with normal glucose tolerance, these measures of adipocyte metabolism were quantified in 10 NIDDM subjects before and after control of hyperglycemia with insulin. The results demonstrate that maximum insulin-stimulated glucose transport (P less than 0.02) and glucose incorporation into triglyceride (P less than 0.01) and CO2 (P less than 0.05) (at 5.5 mM glucose) increased and basal lipolysis decreased (P less than 0.05) after 4 wk of insulin treatment. In contrast, glucose incorporation into lactate and other glycolytic metabolites (at 5.5 mM glucose), and sensitivity of glucose transport to insulin, did not improve with insulin therapy. The latter occurred despite an increase in insulin binding (P less than 0.01). Finally, the improvement in maximal insulin-stimulated glucose transport correlated with the fall in fasting hyperglycemia (r = 0.77, P less than 0.01). These findings demonstrate that several of the abnormalities of carbohydrate and lipid metabolism recently noted to be present in adipocytes from patients with NIDDM can be shown to significantly improve with insulin treatment.