Urinary C-peptide Research Articles

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.

Clinical characteristics of Japanese youth-onset type 2 diabetes with ketonuria

The study analyzed the clinical background and eating habits of Japanese youth-onset type 2 diabetes. Thirty-six patients with type 2 diabetes (22 males, 14 females) with onset in less than 20-year-old were studied. All patients were negative for anti-glutamic acid decarboxylase (GAD) antibody and islet cell antibody. Cases diagnosed as having abnormalities in the mitochondrial gene, maturity onset diabetes of the young (MODY), and apparent type 1 diabetes were excluded from the study. Urinary ketone was detected positive in 11 cases among 36 patients at the onset of diabetes. We compared the clinical characteristics and food compositions between the patients with ketonuria and those without ketonuria. Age and urinary C-peptide secretion did not show any significant difference between both groups. In the patients with ketonuria, male to female ratio was remarkably high (10:1) compared with the group without ketonuria (12:13). Positive diabetic family history was predominantly higher in the group with ketonuria (11/11) than that in the group without ketonuria (17/25). All these were identical to previously reported characteristics of soft-drink ketosis. However, we in this study, revealed the difference of total calorie intake and dietary composition between youth-onset type 2 diabetes with and without ketonuria. As a result dietary contents such as carbohydrate, fat and confectionery in the former group were also 1.5, 1.4–2.4 times higher, respectively, than those in the latter group.

Mecanismos que aceleran el envejecimiento: relación de la resistencia a la leptina con la insulínica

Objectives obesity reduces life potential through increasing aging rates. Leptin and insulin resistance are here especially involved. The former produces impairment of body weight homeostasis, whereas the latter a propensity to develop atherosclerosis. We studied, on the one hand, the relationship of leptinemia with insulin secretion, on the other hand, that of both hormone parameters with food intake and body weight. Patients and method in 38 individuals of both genders with body mass index (BMI) of 35-86, serum leptin, daily insulin secretion through urinary C-peptide, and basal glycaemia under ad libitum diet were determined in basal conditions. Then, under mild hypocaloric diet, a follow up was begun with repetition of the mentioned determinations including BMI, approximately every 6 months during a maximum time of 3.4 years. Results leptinemia is statistically significantly related to BMI, but only in females. Nevertheless, there is a significant correlation between serum leptin and insulin secretion in both gender, but the response of leptinemia to caloric content of diet seems to appear more rapidly than in the case of insulin secretion. The decline in leptinemia following caloric restriction is independent of body weight behaviour, so that this decrease can be observed without any major change in body weight. Comparing the initial values with those at the end of the follow up period under slight caloric restriction, all parameters tend to normalization, but only serum leptin shows a statistically significant clear decrease. Conclusions caloric restriction appears to act directly on the normalization process of hyperleptinemia. Finally, it is postulated that this phenomenon would be part of a sort of repair mechanism to the hypothalamic leptin resistance of obesity, on which indirectly depends, or follows, the recovery of insulin sensitivity linked to weight and glycaemic normalization.

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.

Heterogeneity of early-onset and ketosis-resistant diabetes in Korean subjects—is it possible to determine cut-off age of early-onset type 2 diabetes?

Objective: To investigate the heterogeneity of early-onset and ketosis-resistant diabetes and to define a not-arbitrary cut-off age for early-onset diabetes based on its clinical and metabolic characteristics, and diabetes complications. Methods: We classified 1015 early-onset diabetes subjects aged 21–40 into four groups (group I, age at diagnosis 21–25 years; group II, 26–30; group III, 31–35; group IV, 36–40). Familial and diabetic history, statue of insulin secretion, metabolic parameters, and diabetes complications were analyzed. Results: No significant difference in family history or the rate of diabetic complication was found in the four groups. Subjects with a 21 to a 25-year-old diabetes onset had the lowest serum C-peptide levels, with 50% of the cumulative 24-h urine C-peptide levels of the other three groups ( p < 0.0001). This group also had the lowest prevalence of hyperlipidemia and arterial hypertension ( p < 0.01 and <0.0001, respectively). Group III was found to have a higher prevalence of insulin insufficiency and hypertension than group IV. Conclusion: Our data based on insulin secretory function and metabolic factors might suggest that a cut-off age of 26 years might be warranted in Korean patients. Korean early-onset type 2 diabetes patients tend to be non-obese and insulin secretory dysfunction.

Seroconversion of Glutamic Acid Decarboxylase Antibodies in a Patient Initially Diagnosed as Having Type 2 Diabetes Mellitus

A 61-year-old man admitted in July 1998 had suffered from thirst, polydipsia and polyuria for three years. Diet and transient insulin therapy had induced good blood glucose control which was maintained by metformin hydrochloride for a year. Although it worsened, conventional insulin treatment re-implemented good blood glucose control. Glutamic acid decarboxylase antibodies (GAD-Ab) had been negative up to this point. After 8 months, blood glucose levels became elevated. To date, the GAD-Ab has been positive (112-120 U/ml), and the serum and urine C-peptide levels are decreased. Seroconversion of GAD-Ab should be noted in patients initially diagnosed as having GAD-Ab negative type 2 diabetes mellitus.

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.

Hyperphagia Contributes to the Normal Body Composition and Protein-Energy Balance in HIV-Infected Asymptomatic Men

Wasting can occur at an early stage of HIV infection. Both reduced energy intake and increased resting energy expenditure (REE) have been considered as factors in wasting with predominant lean body mass loss, suggesting disturbances of protein metabolism. Our aim was to study protein-energy metabolism in relation to body composition and oral energy intake in asymptomatic patients with HIV infection but receiving no active antiretroviral therapy. Stable-weight asymptomatic male patients (n = 8) at stage A of HIV infection with a detectable viral load were compared with 9 healthy control men. Protein metabolism was studied in the postabsorptive state using a primed constant infusion of l-[1-(13)C]leucine and l-[2-(15)N]glutamine. REE was studied by indirect calorimetry, body composition by bioelectrical impedance, and energy intake by dietary records. BMI and lean body mass did not differ between patients and controls. In HIV-infected subjects, energy intake, protein breakdown, protein synthesis, and REE were 57% (P < 0.05), 18% (P < 0.05), 22% (P < 0.05) and 14% (P < 0.05) greater than in controls, respectively. REE and protein breakdown were correlated (r = 0.73, P < 0.05). The hormonal profile was normal in HIV-infected subjects with the exception of low urinary C-peptide and plasma reverse triiodothyronine. Plasma interleukin-6 and tumor necrosis factor-alpha were greater than in controls, but energy intake was 1.53 times the REE in the HIV-infected men. Thus, at the asymptomatic stage of HIV infection, increased protein turnover contributes to the increase in the REE. Moderate hyperphagia, which occurred despite increased levels of cytokines, in conjunction with increased protein synthesis maintains a normal body composition, without significant loss of lean body mass.

A case of type 2 diabetes with high levels of plasma and urinary C-peptide

By screening 204 diabetes patients, a male with age 38 was found to have increased C-peptide levels in plasma (over 6ng/ml) and urine (430μg/day), both of which were the highest among the screened subjects. He developed type 2 diabetes at age 31, without history of obesity (weight was 52kg and height 170cm). He had bilateral testicular atrophy. Fasting plasma glucose level was 160mg/dl and HbA1c was 8% at age 38. There was hypertriglycemia (290–662mg/dl). There were no abnormal peaks of IRI or CPR in the serum fractionated by gel filtration (Biogel P 30). Molar ratio of p-CPR/s-IRI was 10.8. Islet cell antibody, anti-insulin binding antibody and anti-insulin receptor antibody were negative. LSH and FSH were both elevated, and free testosterone was decreased. TSH and Leptin levels were elevated. Other laboratory data were within normal range. CT scan revealed fatty liver and horse-shoe kidney. These clinical pictures do not match the criteria to known syndromes associated with diabetes. Although the single case report is insufficient to discuss the C-peptide mechanism of action, this case may give us a hint to understand an aspect of the pathophysiology of C-peptide’s bioactivity dysfunction.

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.

Association between CTLA-4 +49 A/G Polymorphism and Type 1B Diabetes in Japanese Population

+49 A/G polymorphism of CTLA-4 gene has been suggested to be associated with type 1 diabetes in some populations. However, a functional significance of the +49 A/G polymorphism is unknown, because it is believed the polymorphism does not affect the function of the CTLA-4 molecule. In this study, we examined the +49 A/G polymorphism of the CTLA-4 gene in 30 Japanese type 1 diabetic patients (14 type 1B and 16 type 1A) and 40 non-diabetic subjects in a case-control study, and stratified patients according to genotype of the polymorphism. The distribution of genotype frequencies differed between type 1 diabetic patients and controls (p<0.01). When the subjects were subdivided into type 1A and type 1B subgroups, a significant difference in G allele frequency was found only between type 1B patients and controls, whereas G allele frequency tended to be higher in type 1A diabetic patients than controls. Type 1B patients displayed more severe metabolic decompensation (higher plasma glucose concentration, lower urinary C-peptide levels, higher insulin requirement, and higher serum amylase levels), and were found to be more prone to diabetic ketoacidosis than type 1A patients. After stratification by genotype, differences in urinary C-peptide and serum amylase levels between type 1A and type 1B patients were found to be due to differences in the GG genotype subgroup, whereas in the AG subgroup those differences disappeared. In conclusion, the +49 A/G polymorphism of CTLA-4 gene was associated with the occurrence of type 1B diabetes in a Japanese population, and type 1B diabetics with a GG genotype were associated with more severe cell dysfunction than their type 1A counterparts.

Application of a C-peptide electrospray ionization-isotope dilution–liquid chromatography–tandem mass spectrometry measurement procedure for the evaluation of five C-peptide immunoassays for urine

This study applied electrospray ionization-isotope dilution–liquid chromatography–tandem mass spectrometry for the evaluation of five urinary C-peptide immunoassays via split-sample measurements. The immunoassays measured in duplicate in the same run, the comparison method in triplicate over different runs. From the data, the within-run imprecision and the method comparison total RSDs were calculated. Regression analysis revealed on the one hand systematic differences, on the other, an excellent correlation between the test and comparison methods. From the spread of the data around the regression line in comparison with the 95% prediction intervals from the total RSD, sample-related effects and/or specificity problems were apparent and investigated.

Effects of acute, heavy-resistance exercise on urinary peptide hormone excretion in humans.

To examine physical exercise-related changes in urinary excretion of protein/peptide hormones and to correlate modifications with the general increase in post-exercise proteinuria, urine C-peptide, insulin and insulin-like growth factor-I (IGF-I) and their plasma concentrations were measured. Plasma and urinary C-peptide, insulin and IGF-I before (Bex) and at the end (Eex) of physical exercise (a 2.5-hour competition, 102 km) were analysed in 20 young cyclists. At Eex compared with Bex, concentration of urinary C-peptide decreased slightly but significantly (21.3 +/- 2.7 vs. 13.5 +/- 1.7 nmol/l), but urinary insulin and urinary IGF-I concentrations significantly increased at Eex (92.5 +/- 4.2 vs. 131.4 +/- 15.7 pmol/l and 10.0 +/- 2.1 vs. 33.6 +/- 3.8 pmol/l, respectively). Plasma insulin and plasma C-peptide significantly decreased, whereas plasma IGF-I was unchanged. Urinary concentrations of total proteins and creatinine significantly increased. Both Eex urinary C-peptide/urinary protein and urinary C-peptide/urinary creatinine ratios were significantly reduced. The correlation between C-peptide and insulin in plasma was confirmed at Bex as well as Eex, but in urine only at Bex. An increased renal tubular reabsorption of C-peptide at the end of exercise might be suggested, but the expected values considering creatinine excretion were almost three times less. The Eex urinary insulin concentration was higher than expected, considering the circulation levels, but lower when compared with the expected concentration considering creatinine excretion. Physical exercise proteinuria, related to an increased protein filtration and a saturation of the mechanisms responsible for the reabsorption, does not appear similar for all peptide hormones.

Sodium Carbonate is a Useful New Preservative for Collecting 24-hr Urine Samples to Measure Urinary C-peptide

Sodium Carbonate is a Useful New Preservative for Collecting 24-hr Urine Samples to Measure Urinary C-peptide

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.

Sudden onset of diabetes with ketoacidosis in a patient treated with FK506/tacrolimus

We report a 43-year-old man who presented diabetic ketoacidosis 1 year after receiving kidney transplantation. He was a recipient of renal transplantation treated with metyl-prednisolone and tacrolimus regimen. The serum level of tacrolimus was 12.4 ng/ml, and he showed hyperphagia before a month of admission. A week before admission, he was aware of polydipsia, polyuria, and general fatigue. He visited our hospital and was found to have severe hyperglycemia (925 mg/dl), significant ketosis and mild metabolic acidosis (pH 7.341), although he had not been diagnosed as diabetes mellitus. He administrated in our hospital, and was treated with insulin for 5 weeks. He was not obese (BMI=18.2 kg/m 2) and had no family history of type 2 diabetes. He was finally treated with diet therapy alone. The 24 h urine C-peptide secretion on the third hospital day was low (8.4 μg per day). However, no autoantibodies against pancreatic islets were positive, and his insulin secretion was recovered at discharge suggesting that he was not type 1 diabetes. Although, tacrolimus has been reported to cause or worsen diabetes mellitus, the present case suggests that it could cause severe decrease in insulin secretion which leading to diabetic ketoacidosis in lean subject without previous history of diabetes mellitus.

Simultaneous pancreas-kidney and pancreas transplantation.

The discovery of insulin in 1922 changed the treatment of type 1 diabetes mellitus (DM) forever. Insulin was the first effective therapy for type 1 DM; however, its success engendered a terrible paradox for patients with this disease. The use of insulin transformed type 1 DM from a rapidly fatal

Clinical features of a polymorphism of the beta3-adrenergic receptor gene in patients with type 2 diabetes mellitus--a study using a pin-point sequencing method.

The human beta(3)-adrenergic receptor (beta(3)AR) is expressed specifically in adipose tissues, and its activation is activated in brown adipose tissues during thermogenesis and in white adipose tissues during lipolysis. We investigated the relationship between a polymorphism of the beta(3)AR gene and the clinical features of type 2 diabetes mellitus. Studies were conducted in 30 type 2 diabetic patients (15 males and 15 females). Analysis of polymorphisms of the beta(3)AR gene was performed by a pin-point sequencing method using the hair of the subjects. Preperitoneal (P-fat) and subcutaneous fat (S-fat) levels were determined by ultrasonography. We found a Trp(64)Arg allele of the beta(3)AR gene in the hair of 27% of all patients. The patients with this mutation showed a significantly younger onset-age of diabetes than those of the wild type. The body mass index, serum GPT levels, fasting immunoreactive insulin (IRI) and daily urinary C-peptide reaction (CPR) in the mutation group were markedly higher than in the wild type group. The P-fat, serum cholesterol and leptin concentrations tended to be higher in the mutation group. Patients in the mutation group had a significantly higher prevalence of hypertension (80%) compared with those in the wild type group (20%). The present results suggest that the clinical features of diabetic patients with a missense mutation in the beta(3)AR gene are substantially distinct from those of the wild type patients. These specific features include obesity, hyperinsulinemia, hypertension, and an increase in preperitoneal fat.