Type I diabetes manifested solely by 2-h oral glucose tolerance test criteria

The clinical presentation of type 1 diabetes usually involves symptoms such as polyuria and polydipsia. However, investigators in the Diabetes Prevention Trial of Type 1 Diabetes (DPT-1) have detected a group of subjects with type 1 diabetes who have a different phenotype. These subjects are asymptomatic, have normal (<6.1 mmol/l) (group A) or impaired (6.1- <7.0 mmol/l) (group B) fasting glucose, but have 2-h glucose values >11.1 mmol/l on their oral glucose tolerance tests (OGTT). Of the 585 OGTTs performed on islet cell antibody (ICA)-positive relatives with insulin autoantibodies (IAA) or low first-phase insulin response (FPIR), normal glucose tolerance (NGT) was found in 427 subjects; impaired glucose tolerance (IGT) was found in 87 subjects, and diabetes was found by 2-h OGTT criteria alone in 61 subjects. Despite marked differences in 2-h glucose values (NGT 5.8 +/- 1.1 mmol/l, IGT 8.9 +/- 0.9 mmol/l, and group A 13.5 +/- 2.5 mmol/l), there were no significant differences in fasting glucose values among NGT (4.8 +/- 0.5 mmol/l), IGT (5.03 +/- 0.5 mmol/l), and group A (4.99 +/- 0.7 mmol/l) categories. Mean FPIR was higher in subjects with NGT compared with subjects with IGT and subjects diagnosed by 2-h OGTT criteria alone. However, the correlation between FPIR and 2-h glucose value was low (r2 = 0.114). Multivariate analysis demonstrated that additional independent variables provide smaller contributions to the 2-h glucose value. In conclusion, there are asymptomatic type 1 diabetic subjects whose diabetes was diagnosed by the 2-h criteria on OGTT alone. Despite the importance of beta-cell dysfunction in the pathogenesis of type I diabetes, factors other than impaired FPIR must also contribute to postprandial glucose tolerance in these subjects.     

Angiotensin II type 1 receptor gene polymorphism and the response to hyperglycemia in early type 1 diabetes

Recent studies suggest that there is an association between the A1166-->C polymorphism of the angiotensin II type 1 receptor (AGT1R), glycemic control, and the risk of diabetic nephropathy in subjects with type 1 diabetes. Because hypertension and renal hemodynamic function are also related to the risk of diabetic nephropathy and because hyperglycemia can activate the renin angiotensin system, we sought to determine if there is an association between the AGT1R polymorphism, baseline renal and peripheral hemodynamic function, and pressor response to high glucose in subjects with early uncomplicated type 1 diabetes. There were 39 diabetic subjects genotyped for the AGT1R polymorphism by polymerase chain reaction and segregated into 2 groups: those with and those without the C1166 allele (AA and AC/CC). The average age was 27 +/- 1 years, and the mean duration of diabetes was 3.5 +/- 0.6 years. HbA(1c) values were <10% in all subjects and were similar in the 2 groups (8.2 +/- 0.3 vs. 9.1 +/- 0.4%). After a 7-day controlled diet (150 mmol sodium, 1.5-2.0 g x kg(-1) x day(-1) protein), renal hemodynamic function was assessed by inulin and para-aminohippurate clearance during clamped euglycemic conditions (4-6 mmol/l). Mean values for glomerular filtration rates did not differ between groups during euglycemia. In contrast, mean values for renal plasma flow and renal blood flow were significantly greater in the AC/CC group compared with the AA group. Values for mean arterial pressure were similar in the 2 groups, whereas renal vascular resistance was significantly reduced in the AC/CC group. In 20 subjects (10 from each genotype subgroup), hemodynamic function was assessed on a second occasion during controlled clamped hyperglycemia (9-11 mmol/l) after a similar preparatory period. In response to high glucose, plasma renin activity increased in both genotype groups to the same extent, but a pressor response was noted only in subjects with the C1166 allele. Mean arterial pressure increased significantly in the AC/CC subgroup and remained unchanged in the AA subgroup. We conclude that there is an association between the AGT1R A1166-->C polymorphism and renal hemodynamic function in early type 1 diabetes. But more importantly, the pressor response to hyperglycemia is augmented in those diabetic patients with the C1166 allele and may represent a factor that predisposes them to renal injury during periods of inadequate glucose control.     

Blood sugar control reverses the increase in urinary excretion of prostaglandin D synthase in diabetic patients

BACKGROUND/AIMS: We investigated basal levels of serum and urinary lipocalin-type prostaglandin D synthase/beta-trace (L-PGDS) in type-2 diabetic patients and explored whether glycemic control affects L-PGDS status in another 55 diabetic inpatients with normoalbuminuria. METHODS: Fifty-five type-2 diabetic outpatients (HbA1c, 9.14 +/- 0.20%; creatinine (Cr), 85.1 +/- 2.4 micromol/l), and 55 age-matched healthy control subjects were recruited. Serum and urinary levels of L-PGDS were determined with respect to the stage of diabetic nephropathy. The L-PGDS was localized by immunohistochemistry. RESULTS: The urinary L-PGDS index increased in diabetic patients, compared with the controls (234.8 +/- 27.4 vs. 73.8 +/- 7.8 microg/mmol Cr, p < 0.001). Even in normoalbuminuric patients as well as in microalbuminuric patients, urinary L-PGDS indexes were higher than the controls (166.0 +/- 21.1, p < 0.0001 and 338.6 +/- 62.5 microg/mmol Cr, p < 0.0001, respectively), although the serum L-PGDS level was equal to that in the control subjects. Multiple regression analysis revealed that the urinary L-PGDS index was predicted solely by glucose levels and type-IV collagen index, whereas the serum L-PGDS was determined mainly by age and serum Cr. Glycemic control reduced the urinary L-PGDS index towards the normal range in diabetic patients with normoalbuminuria (172.3 +/- 6.6 vs. 118.1 +/- 2.6 (SE) microg/mmol Cr, p < 0.0001). Immunohistochemistry showed that L-PGDS was uniquely present in the renal tubules in diabetes while in nondiabetics, L-PGDS occurred solely in the peritubular interstitium, not in the tubular cells. CONCLUSION: Inadequate glycemic control is responsible for urinary L-PGDS excretion in the diabetic patients. Urinary L-PGDS is useful to predict subclinical renal injury associated with type-2 diabetes.     

Association between the human glycoprotein PC-1 gene and elevated glucose and insulin levels in a paired-sibling analysis

We studied whether there is an association between the single nucleotide polymorphism c.533A>C (K121Q) in the glycoprotein PC-1 gene and features of the metabolic syndrome in case-control and intrafamily association studies in 922 subjects from Finland and Sweden. No difference was observed in the Q allele frequency between control subjects and type 2 diabetic subjects (12.9 vs. 15.1%). The QK genotype was associated with higher fasting plasma glucose (FPG) concentrations than the KK genotype in type 2 diabetic patients (P <0.001) and their relatives (P <0.05). A permutation test of siblings discordant for the QK and KK genotypes also showed that the nondiabetic siblings with the QK genotype had higher FPG (6.1 +/- 2.0 vs. 5.4 +/- 0.6 mmo/l, P <0.001) and fasting insulin (7.0 +/- 3.6 vs. 4.8 +/- 2.6 mU/l, P <0.05) concentrations than the carriers of the KK genotype. In addition, diabetic siblings with the QK genotype had higher systolic blood pressure (147.0 +/- 18.0 vs. 140.0 +/- 18.7 mmHg, P <0.05) and higher fasting (9.9 +/- 3.0 vs. 8.8 +/- 2.8 mmol/l, P <0.05) and 2-h plasma glucose (17.3 +/- 8.5 vs. 12.9 +/- 4.2 mmol/l, P < 0.05) concentrations than the diabetic carriers of the KK genotype. The present study shows that, although the Q allele of the human glycoprotein PC-1 gene is associated with surrogate measures of insulin resistance, it may not be enough to increase the susceptibility to type 2 diabetes.     

Disturbances in beta-cell function in impaired fasting glycemia

In a cross-sectional study, we assessed beta-cell function and insulin sensitivity index (ISI) with hyperglycemic clamps (10 mmol/l) in 24 subjects with impaired fasting glycemia (IFG, fasting plasma glucose [FPG] between 6.1 and 7.0 mmol/l), 15 type 2 diabetic subjects (FPG >7.0 mmol/l), and 280 subjects with normal fasting glycemia (NFG, FPG <6.1 mmol/l). First-phase insulin release (0-10 min) was lower in IFG (geometric mean 541 pmol/l.10 min; 95% confidence interval [CI] 416-702 pmol/l.10 min) and in type 2 diabetes (geometric mean 376 pmol/l.10 min; 95% CI 247-572 pmol/l.10 min) than NFG (geometric mean 814 pmol/l.10 min; 95% CI 759-873 pmol/l.10 min) (P < 0.001). Second-phase insulin secretion (140-180 min) was also lower in IFG (geometric mean 251 pmol/l; 95% CI 198-318 pmol/l; P = 0.026) and type 2 diabetes (geometric mean 157 pmol/l; 95% CI 105-235 pmol/l; P < 0.001) than NFG (geometric mean 295 pmol/l; 95% CI 276-315 pmol/l). IFG and type 2 diabetic subjects had a lower ISI (0.15 plus minus 0.02 and 0.16 plus minus 0.02 micromol/kg fat-free mass [FFM]/min/pmol/l, respectively) than NFG (0.24 plus minus 0.01 micromol/kg FFM/min/pmol/l, P < 0.05). We found a stepwise decline in first-phase (and second-phase) secretion in NFG subjects with progressive decline in oral glucose tolerance (P < 0.05). IFG subjects with impaired glucose tolerance (IGT) had lower first-phase secretion than NFG subjects with IGT (P < 0.02), with comparable second-phase secretion and ISI. NFG and IFG subjects with a diabetic glucose tolerance (2-h glucose >11.1 mmol/l) had a lower ISI than their respective IGT counterparts (P < 0.05). We conclude that the early stages of glucose intolerance are associated with disturbances in beta-cell function, while insulin resistance is seen more markedly in later stages.     

回盲肠间置代幽门术对糖代谢作用的影响

目的研究将回盲肠间置幽门替代术应用于胃肠道重建中的可行性。方法将21例成年健康小型猪分为3组:假手术对照组、BⅠ式组和远端胃大部切除带蒂回盲肠间置幽门替代手术组(回盲肠间置组),在术后60和120d时口服葡萄糖后在0、30、60、90和120min用快速血糖试纸法测血糖浓度,比较胃对流质的排空情况,观察术后动物恢复情况。结果术后2个月,峰值血糖浓度BⅠ式组为(7.8±1.0)mmol/L,回盲肠间置组为(7.1±0.8)mmol/L,假手术对照组为(4.1±0.4)mmol/L;前两组与假手术对照组比较,差异均有非常显著的统计学意义(P<0.01)。4个月后,回盲肠间置组峰值血糖浓度为(5.2±0.8)mmol/L,对照组(4.2±0.5)mmol/L,BⅠ式组(6.9±1.0)mmol/L。回盲肠间置组与假手术对照组比较,差异无统计学意义(P>0.05);但这两组与BⅠ式组比较,差异均有非常显著的统计学意义(P<0.01)。结论回盲肠间置幽门替代术重建消化道具有可行性。     

Diabetes attenuates the hemodynamic stabilizing effects of oral clonidine during off-pump coronary artery bypass surgery

STUDY OBJECTIVE: To investigate the influence of diabetes mellitus on the hemodynamic-stabilizing effect of clonidine during off-pump coronary artery bypass (OPCAB) surgery. DESIGN: Prospective study. SETTING: Public, university-affiliated hospital. PATIENTS: 40 patients (32 male, 8 female) scheduled for OPCAB surgery. INTERVENTIONS AND MEASUREMENTS: Patients were divided into equal groups of diabetic and nondiabetic patients. All patients were given 150 microg oral clonidine 1 hour before induction. Anesthesia was induced and maintained with fentanyl, propofol, and sevoflurane. Propranolol was administered intermittently to maintain an adequate heart rate (HR; 50 to 70 bpm). Preoperative demographic data (fasting blood glucose concentration and hemoglobin A1c), dose of intraoperative drugs (propofol and propranolol), and outcome data (duration of intubation and duration of hospital stay after surgery) were analyzed. MAIN RESULTS: In the diabetic and nondiabetic groups, the mean (+/-SD) plasma glucose values were 7.8 +/- 2.3 mmoL. L(-1) and 5.4 +/- 0.7 mmoL. L(-1), respectively (p < 0.05), and the mean (+/-SD) HbA1c values were 7.1 +/- 1.3% and 5.2 +/- 0.4%, respectively (p < 0.05). The mean propofol infusion rate was 2.8 +/- 0.9 mg. kg(-1). h(-1) in diabetic patients and 3.1 +/- 1.0 mg. kg(-1). h(-1) in nondiabetics (NS, p > 0.05). The total requirement for propranolol was 5.1 +/- 2.4 mg in diabetic patients and 1.6 +/- 1.1 mg in nondiabetics (p < 0.05). CONCLUSIONS: Diabetes attenuates the hemodynamic stabilizing effects of preanesthetic oral clonidine in the clinical setting.     

Ultrafiltration volume is associated with changes in blood pressure in chronically hemodialyzed patients

INTRODUCTION: Volume overload is a main factor in development of hypertension in hemodialysis patients. In order to demonstrate impact of ultrafiltration volume on blood pressure during 15-months period in a group of patients undergoing chronic hemodialysis therapy, we conducted this study. We hypothesized that ultrafiltration volume different affects the pre/postdialysis systolic pressure, diastolic pressure, mean arterial pressure (MAP), and pulse pressure (PP) values. SUBJECTS AND METHODS: Study subjects were 23 anuric chronically hemodialyzed patients. The overall study time was 15 months, and 136 single hemodialysis treatments were analyzed. RESULTS: Ultrafiltration was negatively correlated with predialysis systolic blood pressure (r = -0.169, p = 0.025), postdialysis systolic blood pressure (r = -0.292, p < 0.001), postdialysis MAP (r = -0.186, p = 0.015), predialysis PP (r = -0.290, p < 0.001), and postdialysis PP (r = -0.370, p < 0.001). Ultrafiltration/dry body mass (UF/W) ratio was negatively correlated with predialysis PP (r = -0.222, p = 0.005), postdialysis PP (r = -0.340, p < 0.001), and postdialysis systolic blood pressure (r = -0.243, p = 0.002). We found significant difference in postdialysis PP between dialyses with UF/W ratio < or = 0.05 an dialyses with UF/W ratio > 0.05 (63.49 +/- 20.76 vs. 56.27 +/- 16.33 mmHg, p = 0.033). CONCLUSION: The ultrafiltration volume strongly affects postdialysis PP values. Evaluation of elevated blood pressure treatment in patients undergoing chronic hemodialysis therapy must be considered in respect of postdialysis PP values, not just depending on pre/postdialysis systolic and diastolic pressur or MAP values.     

Insulin secretion and insulin sensitivity in relation to glucose tolerance: lessons from the Botnia Study

Recently, a new stage in glucose tolerance, impaired fasting glucose (IFG) (fasting plasma glucose level of 6.1-6.9 mmol/l), was introduced in addition to impaired glucose tolerance (IGT) (2-h glucose level of 7.8-11.0 mmol/l). It is not clear whether IFG and IGT differ with respect to insulin secretion or sensitivity. To address this question, we estimated insulin secretion (by measuring both insulin levels and the ratio of insulin-to-glucose levels in 30-min intervals) and insulin sensitivity (by using the homeostasis model assessment [HOMA] index) from an oral glucose tolerance test (OGTT) in 5,396 individuals from the Botnia Study who had varying degrees of glucose tolerance. There was poor concordance between IFG and IGT: only 36% (303 of 840) of the subjects with IFG had IGT, whereas 62% (493 of 796) of the subjects with IGT did not have IFG. Compared with subjects with normal glucose tolerance (NGT), subjects with IFG were more insulin resistant (HOMA-insulin resistance [IR] values 2.64 +/- 0.08 vs. 1.73 +/- 0.03, P < 0.0005), had greater insulin responses during an OGTT (P = 0.0001), had higher waist-to-hip ratios (P < 0.005), had higher triglyceride and total cholesterol concentrations (P < 0.0005), and had lower HDL cholesterol concentrations (P = 0.0001). Compared with subjects with IFG, subjects with IGT had a lower incremental 30-min insulin-to-glucose area during an OGTT (13.8 +/- 1.7 vs. 21.7 +/- 1.7, P = 0.0008). Compared with subjects with IGT, subjects with mild diabetes (fasting plasma glucose levels <7.8 mmol/l) showed markedly impaired insulin secretion that could no longer compensate for IR and elevated glucose levels. A progressive decline in insulin sensitivity was observed when moving from NGT to IGT and to subjects with diabetes (P < 0.05 for trend), whereas insulin secretion followed an inverted U-shaped form. We conclude that IFG is characterized by basal IR and other features of the metabolic syndrome, whereas subjects with IGT have impaired insulin secretion in relation to glucose concentrations. An absolute decompensation of beta-cell function characterizes the transition from IGT to mild diabetes.     

骨钙素水平与超重、2型糖尿病、高血压和HDL-C的关联分析

目的探究骨钙素水平与肥胖、2型糖尿病、高血压和高密度脂蛋白之间的相关性。方法选取2015年1月至2017年12月于我院内分泌科确诊的2型糖尿病合并原发性高血压患者82例、体检中心体检结果超重且无高血压以及糖尿病史者129名、诊断为原发性高血压且血糖正常者135例作为研究对象,收集所有研究对象的基本资料,并采取空腹血检查其骨钙素水平、血糖水平、血浆脂质水平,采用多重线性回归探究影响骨钙素水平的相关因素。结果单因素简单线性回归结果表明,骨钙素(osteocalcin,OC)与体质量指数(body mass index,BMI)值、腰围、HbA1c呈正相关,而与收缩压、高密度脂蛋白(HDL-C)呈负相关;多重线性回归结果表明,OC水平与BMI值、HbA1c、收缩压、HDL-C独立相关,其中OC与BMI值和HbA1c呈正相关,而与收缩压、HDL-C呈负相关。结论本研究表明超重和2型糖尿病与OC水平呈独立负相关,收缩压和HDL-C与OC水平呈独立正相关。     

Effect of dietary energy restriction on glucose production and substrate utilization in type 2 diabetes

A total of 8 obese subjects with type 2 diabetes were studied while on a eucaloric diet and after reduced energy intake (25 and then 75% of requirements for 10 days each). Weight loss was 2, 3, and 3 kg after 5, 10, and 20 days, respectively; all of the weight lost was body fat. Fasting blood glucose (FBG) levels fell from 11.9 +/- 1.4 at baseline to 8.9 +/- 1.6, 7.9 +/- 1.4, and 8.8 +/- 1.3 mmol/l at days 5, 10, and 20, respectively (P < 0.05, baseline vs. 5, 10, and 20 days). Endogenous glucose production (EGP) was 22 +/- 2, 18 +/- 2, 17 +/- 2, and 22 +/- 2 pmol x kg(-1) lean body mass (LBM) x min(-1) (P < 0.05, days 5 and 10 vs. baseline). Gluconeogenesis measured by mass isotopomer distribution analysis provided 31 +/- 4, 41 +/- 5, 40 +/- 4, and 33 +/- 4%, respectively, of the EGP (NS); absolute glycogenolytic contribution to the EGP was 15 +/- 2, 11 +/- 2, 11 +/- 2, and 15 +/- 2 pmol x kg(-1) LBM x min(-1), respectively (P < 0.001, baseline vs. days 5 and 10 and day 10 vs. day 20). The blood glucose clearance rate increased significantly at day 20 (P < 0.05). Neither lipolysis nor flux of plasma nonesterified fatty acids were altered compared with baseline. In conclusion, severe energy restriction per se independent of major changes in body composition reduces both FBG concentration and EGP in type 2 diabetes, the reduction in EGP results entirely from a reduction of glycogenolytic input into blood glucose, and the duration of reduced glycogenolysis is short-lived after relaxation of energy restriction even without weight gain, but effects on plasma glucose clearance persist and partially maintain the improvement in fasting glycemia.     

内蒙古呼伦贝尔地区成人慢性肾脏病流行病学调查

目的 探讨我国内蒙古自治区呼伦贝尔少数民族聚居区成年人群中慢性肾脏病（CKD）患病率及其危险因素。 方法 对该地区20岁以上常住居民进行CKD抽样调查,被调查者均检测了尿白蛋白/肌酐比率、血尿（离心后尿沉渣显微镜检查）及估计肾小球滤过率（eGFR,检验血清肌酐后用国人校正的简化MDRD公式计算）;并同时调查了CKD的相关危险因素。 结果 符合入选条件的被调查者共4522例,白蛋白尿阳性率为7.11%;血尿阳性率为2.64%;eGFR低于60 ml&#8226;min-1&#8226;(1.73 m2)-1者为2.75%;去除白蛋白尿、血尿及eGFR下降共同存在造成的重复,该地区CKD患病率为12.95%。高血压患病率38.90%,糖代谢异常6.61%,脂代谢异常34.60%,腰围增大24.79%,代谢综合征15.02%。多因素Logistic回归分析及分层分析显示,年龄增加、腰围增大、收缩压升高、空腹血糖升高、血清三酰甘油增高及患代谢综合征与白蛋白尿发生相关;年龄增加、收缩压升高及空腹血糖升高与肾功能下降相关;年龄增加与血尿发生相关。 结论 内蒙古自治区呼伦贝尔地区CKD患病率为12.95%。相关危险因素包括年龄增加、腰围增大、高血压、血糖或血脂异常、及代谢综合征。     

Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes.

Abnormalities in vascular reactivity in the micro- and macrocirculation are well established in type 2 diabetes. However, little is known about changes in vascular reactivity in those at risk for developing type 2 diabetes. To address this situation, the vascular reactivity in both the micro- and macrocirculation was studied in four age and sex comparable groups: 30 healthy normoglycemic subjects with no history of type 2 diabetes in a first-degree relative (controls), 39 healthy normoglycemic subjects with a history of type 2 diabetes in one or both parents (relatives), 32 subjects with impaired glucose tolerance (IGT), and 42 patients with type 2 diabetes without vascular complications (diabetes). Laser Doppler perfusion imaging was used to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent) and 1% sodium nitroprusside (SNP) (endothelium-independent), whereas high-resolution ultrasound images were used to measure brachial artery diameter changes during reactive hyperemia. Plasma concentrations of endothelin-1 (ET-1), von Willebrand factor (vWF), soluble intercellular adhesion molecule (sICAM), and soluble vascular cell adhesion molecule (sVCAM) were also measured as indicators of endothelial cell activation. The vasodilatory responses to Ach, expressed as percent increase of blood flow over baseline, were reduced in relatives (98 +/- 48, mean +/- SD), IGT (94 +/- 52), and diabetes (74 +/- 45) compared with controls (126 +/- 67) (P < 0.001 controls versus relatives, IGT, and diabetes). The responses to SNP were similarly reduced: controls (123 +/- 46), relatives (85 +/- 46), IGT (83 +/- 48), and diabetes (65 +/- 31) (P < 0.001 controls versus relatives, IGT, and diabetes) as were the responses in the brachial artery diameter during reactive hyperemia: controls (13.7 +/- 6.1), relatives (10.5 +/- 6.7), IGT (9.8 +/- 4.5), and diabetes (8.4 +/- 5.0) (P < 0.01 controls versus relatives, IGT, and diabetes). Women had greater responses than men in both the micro- and macrovascular circulatory tests, but a similar progressive reduction was observed in both sexes with increasing degrees of glucose intolerance. A significant inverse correlation was found between microvascular reactivity and systolic blood pressure, fasting plasma glucose, HDL cholesterol, fasting plasma insulin, and homeostasis model assessment (HOMA) values, an index of insulin resistance. BMI and diastolic blood pressure had a significant inverse correlation only with endothelium-dependent vasodilation. In the macrocirculation, systolic blood pressure, HbA1c, HDL cholesterol, and HOMA had significant correlation with brachial artery diameter changes. Compared with control subjects, ET-1 was significantly higher in all groups, vWF was higher only in the diabetic group, sICAM levels were higher in the IGT and diabetic groups, while sVCAM concentrations were higher in the relatives and those with diabetes (P < 0.05). On stepwise multivariate analysis, age, sex, fasting plasma glucose, and BMI were the most important contributing factors to the variation of vascular reactivity. Addition of all clinical and biochemical measures explained only 32-37% of the variation in vascular reactivity. These results suggest that abnormalities in vascular reactivity and biochemical markers of endothelial cell activation are present early in individuals at risk of developing type 2 diabetes, even at a stage when normal glucose tolerance exists, and that factors in addition to insulin resistance may be operative.     

Impaired beta-cell function, incretin effect, and glucagon suppression in patients with type 1 diabetes who have normal fasting glucose

We have recently described a novel phenotype in a group of subjects with type 1 diabetes that is manifested by glucose >11.1 mmol/l 120 min after an oral glucose load, but with normal fasting glucose levels. We now describe the metabolic characteristics of these subjects by comparing parameters of islet hormone secretion and glucose disposal in these subjects to age-matched nondiabetic control subjects. The patients with type 1 diabetes had fasting glucose, insulin, and glucagon values similar to those of control subjects. Additionally, the insulin secretory response to intravenous arginine at euglycemia was similar in the control and diabetic groups (264 +/- 33.5 and 193 +/- 61.3 pmol/l; P = 0.3). However, marked differences in beta-cell function were found in response to hyperglycemia. Specifically, the first-phase insulin response was lower in diabetic subjects (329.1 +/- 39.6 vs. 91.3 +/- 34.1 pmol/l; P < 0.001), as was the slope of glucose potentiation of the insulin response to arginine (102 +/- 18.7 vs. 30.2 +/- 6.1 pmol/l per mmol/l; P = 0.005) and the maximum insulin response to arginine (2,524 +/- 413 vs. 629 +/- 159 pmol/l; P = 0.001). Although plasma levels of glucagon-like peptide (GLP)-1 and gastric inhibitory peptide (GIP) did not differ between control and diabetic subjects, the incretin effect was lower in the diabetic patients (70.3 +/- 5.4 vs. 52.1 +/- 5.9%; P = 0.03). Finally, there was a lack of suppression of glucagon in the patients after both oral and intravenous glucose administration, which may have contributed to their postprandial hyperglycemia. Glucose effectiveness did not differ between patients and control subjects, nor did insulin sensitivity, although there was a tendency for the patients to be insulin resistant (9.18 +/- 1.59 vs. 5.22 +/- 1.17 pmol.(-1).min(-1); P = 0.08). These data characterize a novel group of subjects with type 1 diabetes manifested solely by hyperglycemia following an oral glucose load in whom islet function is normal at euglycemia, but who have marked defects in both alpha- and beta-cell secretion at hyperglycemia. This pattern of abnormalities may be characteristic of islet dysfunction early in the development of type 1 diabetes.     

The effect of weight loss after bariatric surgery on albuminuria

BACKGROUND: Bariatric surgery achieves long-term weight loss in obese adults with improvement of diabetes and hypertension. Little is known about the effect of this weight loss on renal parameters. METHODS: We performed a retrospective study of 94 obese adults who had Roux-en-Y gastric bypass surgery with a mean 12-month follow-up. Baseline (preoperative) mean age was 49 years, 76% were female, 37 had blood pressure (BP) >or= 140/90 mmHg and 32 had Type 2 diabetes. 73 patients had normoalbuminuria (urine albumin creatinine ratio (ACR) <30 mg/g) while 21 had microalbuminuria (ACR 30<300 mg/g). RESULTS: At follow-up (postoperative), we observed a decrease in mean body weight (133.6 to 97.9 kg, p<0.0001), mean hemoglobin A1c (6.3 to 5.6%, p<0.0001) and mean systolic blood pressure (132.7 to 114.0 mmHg, p<0.0001). There was a significant reduction in ACR (median with interquartile range) from 9.5 (5-28) to 5.5 (3-10) mg/g, p < 0.0001. Fewer patients had microalbuminuria (22.2 to 6.2%, p=0.004) after surgery. Subgroup analysis revealed that significant decrease in ACR was present in the 32 patients with diabetes (16.5 (5-67) to 6.0 (4-11) mg/g, p=0.001) and in the 37 patients with metabolic syndrome (8.0 (5-16) to 6.0 (3-13) mg/g, p=0.012), while 25 patients with obesity alone had a lower ACR (6.5 (4-13) to 4.5 (3-8) mg/g, p=0.270). Multiple linear regression analysis showed change in hemoglobin A1c (p=0.011) and baseline level of ACR (p<0.0001) to be significantly associated with change in ACR. CONCLUSION: We conclude that obese adults have a reduction in albuminuria after surgical weight loss, most importantly in patients with diabetes or metabolic syndrome.     

Red cell Na+/Li+ countertransport in non-insulin-dependent diabetics with diabetic nephropathy

Genetic predisposition to essential hypertension, as indicated by increased maximal velocity of Na+/Li+ countertransport in red cells, has been suggested as a marker for the risk of developing diabetic nephropathy. To evaluate the validity of this concept in non-insulin-dependent diabetics, we measured the maximal velocity of Na+/Li+ countertransport in red cells in 18 male diabetics suffering from proteinuria due to biopsy proven diabetic glomerulosclerosis (GFR: 51 [range 27 to 146] ml/min/1.73 m2), 17 male diabetics with normoalbuminuria, and in 18 sex-, age-, and body mass index-matched healthy control subjects. Na+/Li+ countertransport was identical in patients with and without diabetic nephropathy, 0.43 (0.24 to 0.92) versus 0.44 (0.20 to 0.83) mmol/(liter cells x hr), but was elevated compared to control subjects, 0.32 (0.09 to 0.73; P less than 0.05). Arterial blood pressure was elevated in patients with nephropathy (162/92 +/- 21/9 mm Hg) compared to normoalbuminuric patients (132/82 +/- 15/7) and control subjects (133/83 +/- 14/7 mm Hg; P less than 0.001). Our study does not support the hypothesis that the risk of diabetic nephropathy in non-insulin-dependent diabetes is associated with a genetic predisposition to hypertension. Diabetes per se seems to enhance Na+/Li+ countertransport activity.     

Diabetes and hypertension in South African Indians. A community study

A community survey was done to assess the prevalence of diabetes and hypertension in Indians living in Durban. Each subject, selected by systematic cluster sampling, had blood pressure measured and a glucose tolerance test. Diagnoses of diabetes mellitus and of hypertension were based on World Health Organization criteria. Of the 1,064 subjects studied 9% had diabetes and 14.2% hypertension; diabetes mellitus was more common in women (10.5%) than men (7%), whereas the prevalence of hypertension was similar in both sexes (women 13.5%, men 14.7%). Hypertension was found in 45.8% of the diabetic subjects, 31.4% of those with impaired glucose tolerance and 9.9% of those with normal glucose tolerance. Although hypertension was more common in women (63.3%) than men (37.9%) in the diabetic group, there was no significant difference in the sex distribution in the subjects with impaired glucose tolerance and those with normal glucose tolerance. Of the subjects with hypertension, 29.1% had diabetes; there was no significant difference in the sex distribution. The mean age-adjusted body mass indices were significantly higher in the hypertensive subjects with all degrees of glucose tolerance than in normotensive subjects. There was a trend towards elevation of both systolic and diastolic blood pressure with increasing degrees of glucose intolerance and increasing age.     

Effect of antilipemic therapy on patients with diabetes mellitus and obesity

Fibrates are hypolipemic agents used in noninsulin dependent diabetes mellitus (NIDDM) because these drugs have no influence on glycemia control. The efficiency of fenofibrate (Lipanthyl) was studied in a group of 22 subjects, 30-70 years, obese (body mass index-BMI over 30 kg/m2) or overweight (BMI = 28-30 kg/m2) with hypertension or/and diabetes. All the patients received 200 mg fenofibrate daily, for 6 month, and they had a hypocaloric diet. We measured seric lipids. The results were compared with a control group (20 normal subjects). Under treatment, atherogenic lipids (total cholesterol, LDL-cholesterol and triglycerides) had significantly decreased (p < 0.05) and antiatherogenic fraction (HDL-cholesterol) significantly increased (p < 0.05) compared to initial values. In the mean time, the BMI has significantly decreased under fenofibrate treatment, this body mass loss having a positive influence on lipid metabolism. We observed a better therapeutically response in obese patients vs. the overweight ones, probably due to a higher prevalence of the hypertension in the second subgroup. In conclusion fenofibrate is the drug which can be choose in diabetic dyslipidemia without cardiac disease.     

Mode of onset of type 2 diabetes from normal or impaired glucose tolerance

Fasting plasma glucose concentrations (FPG) predict development of type 2 diabetes. Whether hyperglycemia evolves from normoglycemia gradually over time or as a step increase is not known. We measured plasma glucose and insulin levels during oral glucose testing in 35- to 64-year-old men and nonpregnant women from a population-based survey (Mexico City Diabetes Study) at baseline (n = 2,279) and after 3.25 (n = 1,740) and 7 years (n = 1,711) of follow-up. In subjects with normal glucose tolerance (NGT) on all three occasions (nonconverters; n = 911), FPG increased only slightly (0.23 +/- 0.79 mmol/l, mean +/- SD; P < 0.0001) over 7 years. In contrast, conversion to diabetes among NGT subjects (n = 98) was marked by a large step-up in FPG regardless of time of conversion (3.06 +/- 2.57 and 2.94 +/- 3.11 mmol/l, respectively, at 3.25 and 7 years; P < 0.0001 vs. nonconverters). Likewise, in subjects who converted to diabetes from impaired glucose tolerance (n = 75), FPG rose by 3.14 +/- 3.83 and 3.12 +/- 3.61 mmol/l (P < 0.0001 vs. nonconverters). Three-quarters of converters had increments in FPG above the 90th percentile of the corresponding increments in nonconverters. Converters had higher baseline BMI (30.4 +/- 4.9 vs. 27.3 +/- 4.0 kg/m(2); P < 0.001) and fasting plasma insulin values (120 +/- 78 vs. 84 +/- 84 pmol/l; P < 0.02) than nonconverters; however, no consistent change in either parameter had occurred before conversion. In contrast, changes in 2-h postglucose insulin levels between time of conversion and preceding measurement were significantly (P < 0.0001) related to the corresponding changes in FPG in an inverse manner. We conclude that, within a 3-year time frame, the onset of diabetes is very often rapid rather than gradual and is in part explained by a fall in glucose-stimulated insulin response.     

Effect of physiological hyperinsulinemia on gluconeogenesis in nondiabetic subjects and in type 2 diabetic patients

Gluconeogenesis (GNG) is enhanced in type 2 diabetes. In experimental animals, insulin at high doses decreases the incorporation of labeled GNG precursors into plasma glucose. Whether physiological hyperinsulinemia has any effect on total GNG in humans has not been determined. We combined the insulin clamp with the (2)H(2)O technique to measure total GNG in 33 subjects with type 2 diabetes (BMI 29.0 +/- 0.6 kg/m(2), fasting plasma glucose 8.1 +/- 0.3 mmol/l) and in 9 nondiabetic BMI-matched subjects after 16 h of fasting and after euglycemic hyperinsulinemia. A primed-constant infusion of 6,6-(2)H-glucose was used to monitor endogenous glucose output (EGO); insulin (40 mU. min(-1). m(-2)) was then infused while clamping plasma glucose for 2 h (at 5.8 +/- 0.1 and 4.9 +/- 0.2 mmol/l for diabetic and control subjects, respectively). In the fasting state, EGO averaged 15.2 +/- 0.4 micromol. min(-1). kg(-1)(ffm) (62% from GNG) in diabetic subjects and 12.2 +/- 0.7 micromol. min(-1). kg(-1)(ffm) (55% from GNG) in control subjects (P < 0.05 or less for both fluxes). Glycogenolysis (EGO - GNG) was similar in the two groups (P = NS). During the last 40 min of the clamp, both EGO and GNG were significantly (P < 0.01 or less, compared with fasting) inhibited (EGO 7.1 +/- 0.9 and 3.6 +/- 0.5 and GNG 7.9 +/- 0.5 and 4.5 +/- 1.0 respectively) but remained significantly (P < 0.05) higher in diabetic subjects, whereas glycogenolysis was suppressed completely and equally in both groups. During hyperinsulinemia, GNG micromol. min(-1). kg(-1)(ffm) in diabetic and control subjects, was reciprocally related to plasma glucose clearance. In conclusion, physiological hyperinsulinemia suppresses GNG by approximately 20%, while completely blocking glycogenolysis. Resistance of GNG (to insulin suppression) and resistance of glucose uptake (to insulin stimulation) are coupled phenomena. In type 2 diabetes, the excess GNG of the fasting state is carried over to the insulinized state, thereby contributing to glucose overproduction under both conditions.