Urinary C-peptide Excretion Research Articles

Bilateral dystonia in type 1 diabetes: a case report

IntroductionDiabetic hemichorea-hemiballismus is a rare complication of type 2 diabetes. Here, we report a case with type 1 diabetes, with hemichorea and bilateral dystonia manifested as hyperglycemia-induced involuntary movement.Case presentationA 62-year-old Japanese women with body weight loss of 30 kg during the past year developed symptoms of thirst, polydipsia and polyuria. She also presented with hemichorea and bilateral dystonia for 5 days and extremely high plasma glucose (774 mg/dl), hemoglobin A1c (21.2%) and glycated albumin (100%) with ketosis. Based on the presence of glutamic acid decarboxylase antibodies (18,000 U/ml; normal <1.3 U/ml), low daily urinary excretion of C-peptide (7.8 μg), ketosis and human leucocyte antigen typing DR-4, we diagnosed type 1 diabetes mellitus. We treated the patient with a continuous intravenous regular insulin infusion and medication with haloperidol, and dystonia completely disappeared within 3 days.ConclusionHyperglycemia-induced involuntary movement is one of the manifestations of dystonia and hemichorea-hemiballism.

A case of fulminant type 1 diabetes mellitus after influenza B infection

A 64-years-old man referred to a hospital because of high-grade fever. He was diagnosed as having influenza B by “POCTEM Influenza A/B”, a rapid influenza diagnostic kit which detect some antigens of influenza virus. Six days after medication of oseltamivir phosphate, his flu-symptoms disappeared, but he complained sever thirsty. And after 2 days, he suffered from loss of consciousness and was admitted to the hospital. Laboratory data on admission showed diabetes ketoacidosis, slight elevation of HbA1c level despite sever hyperglycemia, and increase of serum amylase concentration. Anti GAD antibody and anti IA-2 antibody were not detected. Urinary C-peptide excretion was undetectable and serum C-peptide levels were also undetectable after glucagon and arginin load, suggesting disappearance of endogeneous insulin secretion. Class II HLA was susceptible to fulminant type1 diabetes. Based on these findings, we diagnosed him with fulminant type1 diabetes. In Japan, only three viruses in three cases have been reported to be the trigger in the development of fulminant type 1 diabetes. They were human herpes virus 6, herpes simplex virus and Coxsackie B3 virus. This is the fourth report of fulminant type 1 diabetes developed after the established diagnosis of viral infection and the first after influenza B virus infection. The fact that fulminant type 1 diabetes developed after the infection of such a common virus suggest that factors within host will play more important roles than virus itself in the etiology of fulminant type 1 diabetes.

Urinary C-Peptide Excretion in Free-Living Healthy Children Is Related to Dietary Carbohydrate Intake but Not to the Dietary Glycemic Index

This study first examined whether urinary C-peptide (UCP), stored at -20 degrees C, remains stable over the long term, and second, whether the dietary glycemic index (GI) and the glycemic load (GL: GI x g carbohydrates) are related to the 24-h UCP excretion of healthy children. Participants in the Dortmund Nutrition and Anthropometric Longitudinally Designed Study with 24-h urine collections and a simultaneously completed weighed dietary record were included. From these, 3 comparable groups of 7- to 8-y-old children (n = 40 each) from 1990, 1996, and 2002 were randomly selected (total n = 120). C-peptide was measured with a 1-site ELISA. A GI value was assigned to all recorded foods containing carbohydrates (CHO). Statistical equivalence tests corroborated that UCP excretion in the 3 sampling periods was equivalent when corrected for body weight and protein intake (P < 0.05). UCP excretion was associated with the GL after adjustment for body weight, protein, and fiber intake [mean UCP (95% CI) in GL tertiles 1-3: 6.19 (5.37, 7.14) vs. 7.82 (6.77, 9.02) vs. 7.76 (6.71, 8.97) nmol/d, P for difference 0.04]. GI was not significantly related to UCP excretion [adjusted means (95% CI): 7.27 (6.28, 8.41) vs. 6.51 (5.64, 7.51) vs. 7.94 (6.86, 9.18), P for difference 0.2]. In conclusion, UCP retrospectively measured with a 1-site ELISA remained stable for up to 12 y (from 1990 until 2002). The observed positive relation of UCP with GL appears to result largely from its association with the amount of CHO, whereas dietary GI may be relevant only at higher intake levels.

Beneficial effects of nateglinide on insulin resistance in type 2 diabetes

Nateglinide, a rapid insulin secretagogue, is known to facilitate the early phase of insulin secretion and has been used for the treatment of type 2 diabetic patients with postprandial hyperglycemia. The aim of this study is to evaluate the effect of nateglinide on insulin resistance as well as insulin secretory defects in type 2 diabetic patients. Insulin secretion ability was evaluated by the hyperglycemic clamp test, and insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp test, using an artificial pancreas. The hyperglycemic clamp test showed that a 7-day treatment with nateglinide significantly increased insulin secretion in response to high glucose. Interestingly, although nateglinide is known to facilitate insulin secretion, daily urinary C-peptide excretion was decreased after nateglinide treatment. Moreover, in the euglycemic hyperinsulinemic clamp test, glucose infusion rate was significantly increased by nateglinide treatment, indicating that nateglinide functions to decrease insulin resistance. Nateglinide ameliorates insulin resistance as well as insulin secretory defects in type 2 diabetic patients.

Pancreatic exocrine and endocrine events occur concomitantly but independently during the course of fulminant type 1 diabetes

Although pancreatic exocrine enzymes are often elevated in patients with fulminant type 1 diabetes, the onset of this elevation and its significance in disease development remain unclear. We therefore investigated the significance of elevated serum enzyme concentrations and pancreatic swelling in the development of fulminant type 1 diabetes. Serum pancreatic exocrine enzymes, including amylase, elastase-I, lipase and trypsin, were measured during the course of the disease in 11 patients with fulminant type 1 diabetes (3 men and 8 women; a range of age 24–73 years, median 33 years; a range of HbA 1c at onset 4.5–6.7%, median 6.0%), all of whom developed ketotic diabetes requiring intensive insulin therapy within a month. At least one pancreatic exocrine enzyme was elevated in each patient during the course of the disease. The concentration of enzymes on admission could not be correlated with urinary excretion of C-peptide. The time course of increase in serum amylase varied in these patients. In conclusion, neither the level of serum amylase nor the swelling of pancreas was associated with the onset or severity of fulminant type 1 diabetes. The pancreatic exocrine and endocrine events may occur concomitantly but independently during the course of fulminant type 1 diabetes.

Secretin-stimulated Amylase Release into Blood is Impaired in Type 1 Diabetes Mellitus

Prior studies have provided data indicating the existence of close interaction between pancreatic endocrine and exocrine function, but few clinical studies have explored this relationship in depth. We compared pancreatic exocrine function non-endoscopically in individuals with type 1 diabetes mellitus, type 2 diabetes mellitus, and normal glucose tolerant controls, to assess the importance of local insulin production to pancreatic exocrine function. The plasma amylase response to intravenous secretin challenge was measured in men with type 1 diabetes mellitus (n = 5), type 2 diabetes mellitus (n = 5), and normal controls (n = 3). Patients were characterized by their urinary excretion of c-peptide and albumin over 24 hours. Autonomic neuropathy was non-invasively assessed by measuring RR variation (with deep respiration on EKG). Post-secretin amylase responses were generally absent with low baseline levels in the patients with type 1 diabetes mellitus. Patients with type 2 diabetes mellitus and controls showed similar twofold increases over baseline after secretin administration. When normal glucose tolerant and type 2 diabetic patients were pooled and compared against type 1 diabetes mellitus, the differences were statistically significant (p < 0.03). Total amylase response correlated positively, but weakly, with 24 h urinary C-peptide excretion (r = 0.507; p < 0.112), but not with glycemic control, duration of diabetes, or indices of autonomic neuropathy. Patients with type 1 diabetes mellitus, but not type 2 diabetes mellitus, have reduced pancreatic exocrine function, supporting the concept of a local paracrine effect of insulin on pancreatic acinar cells. Further studies are needed to determine the clinical impact of this deficiency, and whether such patients with type 1 diabetes mellitus would benefit from therapy with pancreatic enzyme supplementation.

Insulin resistance in thermally-injured rats is associated with post-receptor alterations in skeletal muscle, liver and adipose tissue.

Several of the possible molecular mechanisms that contribute to the insulin resistance associated with burn injury were examined in a rat model of thermal injury. Rats were subjected to full thickness scald injury (25% total body surface area, 10 sec burn) and resuscitated with saline. After 1, 2 and 3 weeks, urinary C-peptide excretion was measured in burned and sham-treated control animals. At 3 weeks after injury, glucose production by the liver and utilization by skeletal muscle was measured under insulin clamp conditions, insulin receptor binding was measured in skeletal muscle, liver and adipose tissue membranes and IRS-1 expression was measured by Western blot methods. Urinary C-peptide excretion was significantly elevated at 1, 2 and 3 weeks after injury. At 3 weeks after injury, several key metabolic processes were blunted, including the ability of insulin infusion to stimulate glucose uptake by skeletal muscle, the potency of insulin infusion for inhibiting hepatic glucose production, and the ability of a bolus injection of insulin to simulate phosphorylation of IRS-1 in liver, skeletal muscle or adipose tissue. In contrast, there were no apparent alterations in the binding of insulin to membranes from liver, skeletal muscle or adipose tissue. These findings support the concept that the burn injury stimulates insulin production 3 weeks after burn injury, and produces insulin resistance in skeletal muscle, adipose tissue and liver by processes that are associated with post-receptor alterations in the absence of changes in insulin receptor binding.

The Case for a Subcutaneous Magnesium Product and Delivery Device for Space Missions

Cardiovascular (CV) complications, associated with space flight (SF), are caused by microgravity, hypokinesia and radiation, particularly beyond earth orbit, with all three conducive to oxidative stress. Except for emergencies, pharmaceuticals appear to be contraindicated, because of unpredictable side effects from malabsorption (M) and potential hepatic and renal impairment. Magnesium (Mg) depletion and elevations of cytokines (interleukin 6) occur during SF, conducive to self-sustaining vascular inflammation mechanisms. There are potential endothelial injuries (EI) and reduced Cyclic GMP (a second messenger of nitric oxide: NO) and elevated urinary excretion of C-peptide (insulin resistance: IR). Recent findings that show reductions in vascular endothelial growth factor (VEGF) suggest that this may result from SF-related thrombocytopenia since platelets (P) are the major source of VEGF, and that NO might play a role. Both VEGF and Mg are vital for angiogenesis, endothelial function and reendothelialization. Insulin is necessary for VEGF expression. To prevent SF-related CV complications in the presence of IR and M and with the potential for renal insufficiency, closely monitored subcutaneous (SC) Mg should be provided. The dosage can be monitored by sublingual intracellular Mg assays. Needed is development of a SC Mg reservoir device, which can be replenished before extra-vehicular activities (EVA) and which must be reliable despite vigorous movements during EVA, that can last up to 8 hours. This could also be protective against decompression sickness and EVA-related 100% oxygen requirements before and during this activity, both of which predispost to EI.

LDL particle size and lipid composition are risk factors for microalbuminuria in normotensive and normocholesterolemic patients with type 2 diabetes

The study was to evaluate the influence of particle size and lipid composition of low-density lipoprotein (LDL) on urinary albumin excretion and oxidative susceptibility of LDL, and to define association between LDL particle size and α-tocopherol content in LDL from normotensive and normocholesterolemic patients with type 2 diabetes. Twenty-three patients with type 2 diabetes (13 males, 10 females) were studied, and none of these patients had hypertension, hypercholesterolemia and overt proteinuria. The baseline body mass index of all patients was less than 28 kg/m 2. All patients were hospitalized in Hirosaki University Hospital and took dietary therapy whose total intake was restricted to less than 30 kcal/kg of ideal body weight for 3 weeks. Their plasma glucose levels were controlled within fasting plasma glucose <140 mg/dl and 2-h postprandial plasma glucose <200 mg/dl. LDL particle size was evaluated by using high-resolution polyacrylamide gel electrophoresis (Lipoprint LDL™ System) and expressed by Rf value. LDL was incubated with 0.25 μM CuSO 4 for 20 h, and the degree of LDL oxidation was determined by malondialdehide analysis. Twenty-four-hour urinary C-peptide excretion and plasma triglyceride concentration in patients with microalbuminuria were significantly higher than those in normoalbuminuric patients. Rf values in microalbuminuric patients were significantly greater than those in normoalbuminuric patients. There were significantly inverse correlations between Rf value and α-tocopherol content in LDL, and between Rf value and LDL-free cholesterol/LDL-total cholesterol. Thiobarbituarte-reactive substance level in LDL had a tendency to correlate with Rf value and significantly inverse correlation to α-tocopherol content in LDL. In type 2 diabetics without hypertension, hypercholesterolemia and obvious obesity, smaller LDL particle size, accompanied by mild hyperinsulinemia and mild hypertriglyceridemia seems to be one of the important factors responsible for microalbuminuria. In addition, the present study suggests that the decrease of α-tocopherol content in small LDL particle is associated with oxidative susceptibility to Cu 2+-induced oxidation.

Clinical and genetic characteristics of GAD-antibody positive patients initially diagnosed as having type 2 diabetes

The present study was conducted to clarify the clinical and genetic characteristics of the diabetic patients who have antibodies to glutamic acid decarboxylase (GADab) but are diagnosed initially as type 2 diabetes because of the slow progression. Fifty-five GADab + patients and 137 GADab − patients were recruited. The GADab + patients were divided into two subgroups according to their antibody titers. The high-titer subgroup (Ab≥20 U/ml) had lower urinary C-peptide concentrations, and was assigned insulin therapy more often than the GADab − patients. In contrast to the high-titer subgroup, clinical parameters in the low-titer subgroup were similar to the GADab − diabetic patients. The urinary C-peptide levels correlated negatively with the GADab titer in the GADab + patients. Analysis of type 1 diabetes-susceptible HLA alleles revealed high frequencies of the B54 and DRB1*0405 allele, but not the B61 and DRB1*0901 alleles, in the high-titer subgroup, whereas the frequency of the protective DRB1*1502 allele was decreased. The GADab + patients with the B54 allele had higher GADab titers and lower urinary C-peptide excretion than patients without this allele. These data indicated that patients with a high-GADab titer share the autoimmune background characteristic of type 1 diabetes.

Clinical and genetic characteristics of GAD-antibody positive patients initially diagnosed as having type 2 diabetes*1

The present study was conducted to clarify the clinical and genetic characteristics of the diabetic patients who have antibodies to glutamic acid decarboxylase (GADab) but are diagnosed initially as type 2 diabetes because of the slow progression. Fifty-five GADab+ patients and 137 GADab− patients were recruited. The GADab+ patients were divided into two subgroups according to their antibody titers. The high-titer subgroup (Ab≥20 U/ml) had lower urinary C-peptide concentrations, and was assigned insulin therapy more often than the GADab− patients. In contrast to the high-titer subgroup, clinical parameters in the low-titer subgroup were similar to the GADab− diabetic patients. The urinary C-peptide levels correlated negatively with the GADab titer in the GADab+ patients. Analysis of type 1 diabetes-susceptible HLA alleles revealed high frequencies of the B54 and DRB1*0405 allele, but not the B61 and DRB1*0901 alleles, in the high-titer subgroup, whereas the frequency of the protective DRB1*1502 allele was decreased. The GADab+ patients with the B54 allele had higher GADab titers and lower urinary C-peptide excretion than patients without this allele. These data indicated that patients with a high-GADab titer share the autoimmune background characteristic of type 1 diabetes.

Lipoprotein lipase (LPL) mass in preheparin serum reflects insulin sensitivity

Lipoprotein lipase (LPL) is one of the enzymes regulated by insulin and its plasma activity reflects insulin sensitivity. Although intravenous heparin injection is required to measure LPL activity, we can detect LPL mass in preheparin serum (Pr-LPL mass) by immunoassay. In this study, we examined whether Pr-LPL mass reflects insulin sensitivity. We measured Pr-LPL mass, insulin sensitivity (Si), and acute insulin release in response to a glucose bolus (AIRg) in subjects with normal glucose tolerance (NGT; n=23), impaired glucose tolerance (IGT; n=10), and Type II diabetes mellitus (DM; n=48). Si and AIRg were determined by minimal model analysis. We also compared Pr-LPL mass with the homeostasis model assessment of insulin resistance (HOMA-R) and the urinary excretion of C-peptide (urine CPR). We found that Pr-LPL mass correlated significantly with Si ( r=0.354, P<0.01) in all the subjects. This correlation was still significant in the NGT group ( r=0.472, P<0.05), DM group ( r=0.311, P<0.05), and DM group with a fasting plasma glucose >150 mg/dl ( n=20, r=0.459, P<0.05). Moreover, Pr-LPL mass correlated negatively with HOMA-R ( r=−0.272, P<0.05) and fasting IRI ( r=−0.256, P<0.05). By contrast, Pr-LPL mass was not correlated with either urine CPR or log AIRg that reflect the ability to secrete insulin. In conclusion, Pr-LPL mass reflects insulin sensitivity. We speculate that Pr-LPL mass might be used to assess insulin sensitivity not only in the general population but also in advanced diabetic patients.

Glycemic index: overview of implications in health and disease , , ,

The glycemic index concept is an extension of the fiber hypothesis, suggesting that fiber consumption reduces the rate of nutrient influx from the gut. The glycemic index has particular relevance to those chronic Western diseases associated with central obesity and insulin resistance. Early studies showed that starchy carbohydrate foods have very different effects on postprandial blood glucose and insulin responses in healthy and diabetic subjects, depending on the rate of digestion. A range of factors associated with food consumption was later shown to alter the rate of glucose absorption and subsequent glycemia and insulinemia. At this stage, systematic documentation of the differences that exist among carbohydrate foods was considered essential. The resulting glycemic index classification of foods provided a numeric physiologic classification of relevant carbohydrate foods in the prevention and treatment of diseases such as diabetes. Since then, low-glycemic-index diets have been shown to lower urinary C-peptide excretion in healthy subjects, improve glycemic control in diabetic subjects, and reduce serum lipids in hyperlipidemic subjects. Furthermore, consumption of low-glycemicindex diets has been associated with higher HDL-cholesterol concentrations and, in large cohort studies, with decreased risk of developing diabetes and cardiovascular disease. Case-control studies have also shown positive associations between dietary glycemic index and the risk of colon and breast cancers. Despite inconsistencies in the data, sufficient, positive findings have emerged to suggest that the dietary glycemic index is of potential importance in the treatment and prevention of chronic diseases.

C-Peptide Determinations in Islet Xenotransplantation: A Study in the Pig-to-Mouse Model

Assays of C-peptide are used to monitor allogeneic islet graft function. However, it is not known whether xenogeneic C-peptide is metabolized and excreted in a fashion similar to endogenous and allogeneic C-peptide. In this study, injection of 10 times the physiological amount of porcine C-peptide into mice did not result in the excretion of the C-peptide in the urine. In contrast, when a physiological amount of porcine C-peptide was injected into athymic mice, urinary excretion of porcine C-peptide was readily detected. After injection of radioactively labeled porcine C-peptide into mice, the radioactive uptake in tissues belonging to the mononuclear phagocytic system was significantly increased in mice immunized towards the xenogeneic C-peptide. These results may reflect an immunological reactivity towards the C-peptide. Antibodies against porcine C-peptide could not be detected in the serum of any of the mice. However, porcine C-peptide was found to be glycosylated. Thus, a possible explanation to the lack of porcine C-peptide in the urine is that xenoreactive antibodies had bound to carbohydrate structures on the peptide and that the antibody-C-peptide complex had been cleared from the circulation by the mononuclear phagocytic system. Thus, the urinary excretion of xenogeneic C-peptide seems to be different from that of endogenous and allogeneic C-peptide. Consequently, determinations of donor-specific C-peptide may not properly reflect islet xenograft function. In fact, islet xenograft function may be underestimated.

Different clinical characteristics between high and low melatonin excretors in depression

We evaluated the progression of microangiopathic lesions in 22 type I diabetic patients with residual C-peptide excretion and in 22 type I diabetic patients matched for age at onset and disease duration without residual C-peptide excretion. We also wished to elucidate whether certain HLA-DR phenotypes were associated with preserved insulin secretory activity and/or microvascular lesions. The two groups of patients were investigated in 1984 and 1985. In the previous report, we observed less frequent signs of early microangiopathic lesions in association with a lower HbA1c in the group with a detectable urinary C-peptide excretion. The HbA1c level has been measured regularly (7–12 times) since the initial investigation; the mean value was lower in the patient group with residual C-peptide excretion than in the non-C-peptide group (p = 0.01). Nine of the patients in the group without urinary C-peptide excretion had increased severity of retinopathy, but only two in the group with urinary C-peptide excretion (p = 0.04) had progression of retinopathy. Incipient and/or manifest albuminuria was observed in six of the nonexcretor group and one of the C-peptide excretors. Four of the patients were receiving antihypertensive treatment and three others had a diastolic blood pressure ≥ 90 mmHg in the non-C-peptide excretor group as compared with one with a pressure ≥ 90 mmHg in the C-peptide excretor group. All 16 patients with moderate to advanced nonproliferative background retinopathy and/or incipient albuminuria had HLA-DR 34, 3x, or 4x antigens, as compared with 20 of 28 patients with few if any signs of microangiopathy. We conclude that urinary C-peptide excretion together with regular measurements of HbA1c may be used for prognostic evaluation of the increase in severity of retinopathy in groups of patients with type I diabetes.

Mitochondrial DNA Mutations Are Associated with Both Decreased Insulin Secretion and Advanced Microvascular Complications in Japanese Diabetic Subjects

To assess the roles of various mitochondrial (Mt) DNA mutations in diabetic and nondiabetic subjects, we screened Mt DNAs at the 3243 base pair (bp) and its adjacent portion in unrelated Japanese diabetic and nondiabetic subjects. Furthermore, to clarify the clinical features of diabetic subjects harboring a Mt DNA mutation, we evaluated the ability of insulin secretion and microvascular complications in diabetic subjects. Five hundred thirty-seven diabetic patients and 612 unrelated nondiabetic subjects were recruited into this study. In Mt DNA analyses, Mt DNA was isolated from peripheral leukocytes of the subjects, and then an Mt DNA fragment surrounding the tRNA Leu(UUR) site was amplified by the polymerase chain reaction (PCR) using two sets of primers. These fragments were further digested with three kinds of restriction endonucleases and were subjected to agarose gel electrophoresis. When a mutation was present, Mt DNA fragments were directly sequenced with an autosequencer. Baseline characteristics in all subjects were examined, and microvascular complications and insulin secretory capacity in diabetic subjects were newly evaluated. Eight kinds of Mt DNA mutations, which were point mutations, were found in 74 subjects. Each affected subject had only one mutation in the Mt DNA examined. Among them, the mutations at np 3316, 3394, 3593, and 3391 were accompanied by amino acid replacement. Thirty-eight diabetic patients were affected (7.1%), including two subjects with a point mutation at np 3243, and 26 nondiabetic subjects were affected (4.2%). Thus, there was a higher prevalence in diabetic subjects than in nondiabetic subjects. There was no significant difference in the prevalence of maternally inherited diabetes between these two groups. The mean level of urinary C-peptide excretion was lower in diabetic subjects with an Mt DNA mutation (DM+) than in those without it (DM−). Although the prevalence of hypertension in DM+ was higher than that in DM−, diabetic retinopathy and nephropathy in DM+ were problematic, in comparison with those in DM−, when statistical corrections were performed for the effect of hypertension. Furthermore, a strategy based on logistic regression analysis revealed that advanced retinopathy and decreased urinary C-peptide excretion in all diabetic subjects studied were strongly related to the presence of Mt DNA mutation. Our results suggest that Mt DNA mutations in Japanese diabetic subjects are related to the development of diabetes, and also that these mutations are associated with not only a decrease in insulin secretion but also advanced diabetic microvascular complications.

Effect of Adding a Sulfonylurea in Patients with Non-Insulin-Dependent Diabetes Mellitus Previously Well Controlled with Insulin

To determine whether insulin-requiring patients with non-insulin-dependent diabetes mellitus (NIDDM) and good glycemic control would benefit in weight control, serum lipid concentrations, or blood pressure from a reduction in exogenous insulin treatment. Eighteen patients with well-controlled NIDDM who required insulin therapy were entered into a randomized, placebo-controlled, double-blind, crossover study of the addition for 12 weeks of treatment with a second-generation sulfonylurea agent (micronized glyburide). The mean fasting plasma glucose at entry was 7.00 +/- 0.22 mmol/L and at the end of the 12-week treatment phase was 7.67 +/- 0.39 mmol/L with placebo and 7.28 +/- 0.44 mmol/L with active drug. Hemoglobin A(1c) was unchanged during the study (7.5 +/- 0.2% at entry, 7.5 +/- 0.3% with placebo, and 7.4 +/- 0.3% with active drug). Addition of the orally administered agent resulted in a 29% decrease in exogenous insulin requirements and a 37% increase in 24-hour urinary C-peptide excretion. Patients had no change in weight after 12 weeks of either placebo or active drug. Plasma cholesterol levels declined slightly during the study, but they did not differ significantly during drug and placebo treatment. Blood pressure was unchanged in both the subjects with and without hypertension. In patients with NIDDM and good glycemic control with insulin treatment, a glyburide-related increase in endogenous insulin secretion caused a proportionate decrease in exogenous insulin requirements. With continued good glycemic control, however, the orally administered agent showed no additional benefit on weight, blood pressure, plasma triglycerides, or low-density lipoprotein or high-density lipoprotein cholesterol.

Diabetes mellitus associated with the 3243 mitochondrial tRNA Leu(UUR) mutation: Insulin secretion and sensitivity

To investigate the pathophysiology of diabetes mellitus associated with the 3243 mitochondrial tRNA Leu(UUR) mutation (DM-Mt3243), insulin secretion and sensitivity were studied using the 75-g oral glucose tolerance test (oGTT), 1-mg intravenous glucagon test, and euglycemic glucose clamp test. Twelve DM-Mt3243 patients were investigated (seven men and five women). Their ages ranged from 36 to 74 years, and the onset of diabetes occurred at 44.5 ± 9.5 years (mean ± SD). In the glucose tolerance test, nine patients (75.0%) showed lower C-peptide reactivity (CPR) than normal at 30 minutes, suggesting blunted insulin secretion. Three patients showed an impaired glucose tolerance (IGT) pattern, although they had absolute hyperglycemia at the onset of diabetes. In the glucagon test, 10 patients (76.3%) had CPR within the normal range at 6 minutes, indicating an adequate response. In the glucose clamp test, the M value was 8.70 ± 2.35 mg/kg/min and was within normal limits in all patients. The glucose metabolized (M value) was negatively correlated with 24-hour urinary C-peptide excretion ( r = .696, P < .05). Thus, plasma CPR to glucose loading was blunted in many DM-Mt3243 patients, but CPR to glucagon was relatively well preserved. This difference in the intrinsic insulin response to the two stimuli may be characteristic of DM-Mt3243. Although M values were normal in all subjects, the correlation with 24-hour urinary C-peptide excretion suggests a relationship between insulin sensitivity and insulin secretion. These two mechanisms may cooperate to maintain homeostasis in this disease. Since three patients did not progress with aging, this mutation may not always cause gradual β-cell destruction.

The Relationship of Hyperinsulinemic State to Left Ventricular Hypertrophy, Microalbuminuria, and Physical Fitness in Borderline and Mild Hypertension

The relationship of the hyperinsulinemic state to left ventricular hypertrophy, left ventricular geometric patterns, microalbuminuria, and physical fitness were studied in 52 middle-aged unmedicated men with borderline and mild hypertension. Left ventricular mass index and relative wall thickness were assessed by echocardiography. Physical fitness was determined by symptom-limited maximal treadmill stress testings. The urinary concentration of microalbumin and C-peptide was measured in 24-h urine samples by radioimmunoassey. The 24-h urinary C-peptide excretion rate was correlated with left ventricular mass index (r = 0.46), relative wall thickness (r = 0.41), treadmill time (r = −0.35), normalized treadmill time (r = −0.52), systolic blood pressure at peak exercise (r = 0.29), and 24-h urinary microalbumin excretion (r = 0.48). Stepwise multiple regression analysis identified the left ventricular mass index, the 24-h urinary albumin excretion, and the normalized treadmill time as variables in the equation for the 24-h urinary C-peptide excretion. Thus, the hyperinsulinemic state is related to left ventricular hypertrophy, microalbuminuria, and impaired physical fitness in patients with borderline and mild hypertension.

Growth hormone does not prevent catabolic side effects of dexamethasone in extremely low birth weight preterm infants with bronchopulmonary dysplasia--a pilot study.

Recombinant human growth hormone (rhGH) may reduce the catabolic side effects of steroid therapies on children and adults, but this has never been studied in preterm infants. We performed a pilot study on 5 extremely low birth weight preterm infants (gestational age 27 +/- 3 wks, birth weight 824 +/- 160 g) still on mechanical ventilation for bronchopulmonary dysplasia at the postnatal age of 35 +/- 9 days. All were treated for 7 days with dexamethasone (0.5 mg/kg/d i.v.) and subcutaneous rhGH at different doses: 0.1 (n = 1), 0.2 (n = 2) or 0.3 (n = 2) IU/kg/day. Nutrition was kept stable. After 7 days all subjects improved their respiratory condition but body weight remained the same and urinary urea nitrogen and C-peptide were significantly higher (p < 0.001). rhGH intake strongly related to urinary excretion of urea nitrogen (r = 0.78) and C-peptide (r = 0.88). Dexamethasone improves the pulmonary function of very preterm infants with bronchopulmonary dysplasia but induces growth arrest and catabolism which are not prevented, and may be worsened, by rhGH.