C-peptide Excretion Research Articles

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.

Permanent neonatal diabetes mellitus: clinical presentation and epidemiology in Oman

AIMTo estimate the accurate incidence and prevalence of permanent neonatal diabetes mellitus, and to determine the clinical profile of this condition in the Sultanate of Oman.METHODSAll children diagnosed as having...

No evidence of infection with porcine endogenous retrovirus in recipients of porcine islet-cell xenografts

The study of whether porcine xenografts can lead to porcine endogenous retrovirus (PERV) infection of recipients is critical for evaluating the safety of pig-to-man xenotransplantation. PERV is carried in the pig germline, and all recipients of porcine tissues or organs will be exposed to the virus. We studied 10 diabetic patients who had received porcine fetal islets between 1990 and 1993, looking for evidence of PERV infection by using PCR serology, PCR, and reverse transcriptase assays. Prolonged xenograft survival (up to a year) was confirmed in five patients by porcine C-peptide excretion and detection of pig mitochondrial DNA (mtDNA) in serum. Despite the evidence for extended exposure to pig cells and despite concomitant immunosuppressive therapy, we were unable to detect markers of PERV infection in any patient. Screening for two PERV sequences in peripheral blood lymphocytes collected 4-7 years after the xenotransplantation was negative. Markers of PERV expression, including viral RNA and reverse transcriptase, were undetectable in sera from both early (day 3 to day 180) and late (4-7 years) time points. Western blot analysis for antibodies was consistently negative. These results suggested the absence of PERV infection in these patients. Also this study establishes a minimum standard for post-transplant surveillance of patients given porcine xenografts.

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.

Insulin Secretion in Non-obese NIDDM

We investigated the association of the maximal body mass index in the past (max BMI) with insulin secretion in non-obese NIDDM. The study subjects were 42 diabetic inpatients who were treated by diet therapy alone and whose diabetes was well controlled [fasting plasma glucose (FPG) on admission≤120 mg/dl]. We measured the fasting and 2-hour postprandial serum C-peptide levels (FCPR, 2hCPR), daily urinary excretion of C-peptide (UCPR) and fasting serum lipid levels in the diabetics with 20.0≤BMI<24.0 at hospitalization. Patients were classified as obese DM (OB, n=15) if their max BMI was 26.4 or over, and if not, they were classified as non-obese DM (non-OB, n=27). The two groups did not differ in age, duration of diabetes mellitus, BMI, FPG or glycated hemoglobin on admission. FCPR, UCPR and serum triglyceride in OB were significantly lower than in non-OB. Multiple regression analysis indicated that BMI and max BMI were significantly related to FCPR, 2hCPR and UCPR. FCPR and UCPR were each positively related to the serum triglyceride level (r=0.568, p<0.01; r=0.560, p<0.01).These results indicate that endogenous insulin secretion and the serum triglyceride level in OB decrease more than in non-OB.

Correlation between pancreatic endocrine and exocrine function and characteristics of pancreatic endocrine function in patients with diabetes mellitus owing to chronic pancreatitis.

Pancreatic endocrine capacities are remarkably disturbed in patients with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of acinar cell and ductal cell function closely correlate with endocrine function (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes). We sought to clarify the differences of pancreatic endocrine function between pancreatic diabetes and primary diabetes, and to verify the correlations between pancreatic exocrine and endocrine dysfunction in patients with chronic pancreatitis. Urinary C-peptide (CPR) excretion and fasting plasma glucagon levels in patients with pancreatic diabetes owing to calcific pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were studied in comparison with those in patients with insulin-dependent diabetes mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and in healthy controls (11 cases). In addition, pancreatic exocrine function was investigated in patients with chronic pancreatitis (calcific and noncalcific) and in healthy controls. The correlation between pancreatic exocrine and endocrine function was studied. The urinary CPR excretion in controls was 94.9 +/- 20.5 micrograms/d. The urinary CPR excretion in calcific pancreatitis was 12.8 +/- 7.4 micrograms/d and it resembled that in IDDM (9.4 +/- 5.8 micrograms/d). The urinary CPR excretion in noncalcific pancreatitis was 41.5 +/- 30.1 micrograms/d, being similar to that in NIDDM (49.3 +/- 21.0 micrograms/d). The plasma glucagon level in calcific pancreatitis was 64.1 +/- 15.9 rho g/mL, which was significantly lower than the values in IDDM (111.2 +/- 50.2 rho g/mL) and NIDDM (96.7 +/- 21.9 rho g/mL). The plasma glucagon level in calcific and noncalcific pancreratitis (88.4 +/- 29.6 rho g/mL) were significantly lower than that in controls (129.8 +/- 21.6 rho g/mL). The residual capacities of acinar cells and ductal cells were strongly correlated with urinary CPR excretion and plasma glucagon concentration.

A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion of dehydroepiandrosterone sulfate

To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol l-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3α-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 ± 1.5, 6.8 ± 1.8, and 6.9 ± 2.1 μmol/L for B, P, and M, respectively) and urinary excretion (8.8 ± 9.8, 9.4 ± 11.2, 8.0 ± 8.3 gmmol/d) of DHEAS remained unaffected. Considering the clear increments ( P < .01) in urinary C-peptide excretion with diet P (20.4 ± 10.3 nmol/d) versus diets B and M (12.6 ± 5.1 and 13.2 ± 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.

Effects of insulin administration on β-cell function in subjects at high risk for type I diabetes mellitus

The aim of the study was to determine the appropriate dose of subcutaneous insulin to induce “β-cell rest” without any hypoglycemic risk, as the first step in the investigation of its potential effect in preventing or delaying clinical diabetes mellitus onset in high-risk subjects. Four subjects at high risk for type I diabetes mellitus (first-degree relatives, islet cell antibodies (ICA)-positive, and with diminished first-phase insulin secretion) were compared with four healthy individuals. After hospitalization, urinary C-peptide excretion (UCP) and 24-hour serum profiles for glucose were measured before and after administration of NPH insulin 0.1, 0.2, and 0.3 U · kg body weight per day subcutaneously in a single dose on 4 consecutive days. After insulin 0.1 U · kg body weight, a significant inhibition of endogenous insulin secretion was observed in high-risk subjects, but not in control subjects. There was no further inhibition when a higher insulin dose (0.2 and 0.3) was administered. A sustained β-cell rest was obtained after 3, 6, and 12 months of treatment with 0.1 U · kg body weight per day as outpatient therapy in high-risk subjects. With this dose, no subject developed hypoglycemia (plasma glucose <50 mg/dL), whereas this adverse effect was detected after 0.2 and 0.3 U · kg body weight in both groups. In conclusion, our results indicate that administration of NPH insulin 0.1 U · kg body weight per day induces β-cell rest without the undesirable effect of hypoglycemic episodes. This is a preliminary study to investigate the potential beneficial effect of insulin in preventing or delaying type I diabetes mellitus in subjects at high risk for the disease.

Effect of manidipine and delapril on insulin sensitivity in type 2 diabetic patients with essential hypertension

The open trial was designed to evaluate the effects of long-term antihypertensive treatment with the calcium-channel blocker, manidipine and the angiotensin converting enzyme (ACE) inhibitor, delapril on insulin sensitivity in Japanese non-insulin dependent diabetes mellitus (NIDDM) patients with essential hypertension. We measured the insulin sensitivity index (S I) and the glucose-effectiveness (S G) by the use of Bergman's minimal model method in 18 hypertensive NIDDM patients before and after administration of manidipine (group A) or delapril (group B) for 3 months. Manidipine treatment for 3 months significantly improved S I in group A from 3.35 ± 0.61 (× 10 −4 min −1 μU −1 ml −1) to 4.70 ± 1.34 ( P < 0.05). Delapril treatment for 3 months also significantly improved S I in group B from 3.56 ± 1.04 to 5.00 ± 0.87 ( P < 0.05). Manidipine significantly improved S G in group A from 1.60 ± 0.64 (× 10 −2 min) to 2.19 ± 0.38 ( P < 0.05). Delapril treatment also significantly improved S G in the group B from 1.41 ± 0.56 to 1.91 ± 0.35 ( P < 0.05). Manidipine and delapril did not affect urinary C-peptide excretion for 24 h in the hypertensive NIDDM patients. Treatment with manidipine or delapril significantly reduced systolic and diastolic blood pressures in the hypertensive NIDDM patients. There were no differences between plasma glucose, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions, heart rate and body weight after 3 months on manidipine or delapril. This study confirmed the improving effects on S I and S G by long-term treatment with manidipine or delapril in the hypertensive NIDDM patients.

Increase in insulin secretion with age: its clinical importance in evaluating abnormal secretions focused on diabetes type II and obesity.

The urinary C-peptide excretion was measured in a healthy standardized population sample of 160 subjects from 20 to 90 years of age, homogeneously distributed by age and sex. Urinary C-peptide excretion corresponded to 7% of the total amount released. The daily C-peptide excretion was 61.23 +/- 2.2 (S.E.) microg in the whole sample which corresponds to 41.9 +/- 1.5 IU of insulin secreted/day (I(CP)d), without sex differences. There is an increase of the I(CP)d value from the young to the healthy middle-aged person, but when the results were corrected for standard amounts of excreted creatinine (1 g) and urea (22 g) the age-dependent increase is to be observed during the whole adult life span. Assuming that cross-sectionally observed data are representative of the individual changes, it is concluded that age alone increases insulin secretion. The results which may be useful as reference values for clinical application were as follows: (A) in 5 diabetes type II patients in which the I(CP)d value was measured several times a week, the intraindividual variation coefficient was 10.9 +/- 7.2%;(B) in a sample of 47 type II diabetic patients of both sexes, between 51 and 70 years of age, a clear correlation was found between I(CP)d and the results of the glucagon stimulation test, mainly regarding the relationship between I(CP)d and the planimetrically measured area under the curve (r = 0.7, P < 0.0001); (C) in 7 obese non-diabetic individuals of similar ages the influence of the hypocaloric diet on the I(CP)d value was more evident than the use of C-peptide blood determinations before or after glucagon. Finally, the I(CP)d values of type II diabetes patients with insulin requirement (n = 27) were significantly lower than in the healthy control group (31.1 +/- 24.0 vs. 45.0 +/- 20.4), while diabetic patients without insulin requirement showed significantly higher values (73.0 +/- 33.0) (n = 27). These clinical studies primarily focused on the physiology of human ageing justify the measurement of C-peptide urinary excretion for evaluating daily insulin secretion in patients with type II diabetes.

Renal metabolism of C-peptide in patients with early insulin-dependent diabetes mellitus.

Renal metabolism of C-peptide was studied in 6 patients with early insulin-dependent diabetes mellitus (IDDM) with residual beta cell activity and in 11 nondiabetic subjects by the arterial-venous difference technique both in the postabsorptive state and for 80 min after ingestion of an amino acid mixture (0.8 g/kg). Urinary C-peptide (Cp) excretion, glomerular filtration rate and renal plasma flow were also measured. In the postabsorptive state in IDDM, renal uptake of Cp is reduced, while its urinary excretion and clearance are significantly increased. As a result, net renal extraction is markedly reduced. In contrast to controls, renal uptake and net extraction of C-peptide after amino acid ingestion do not increase in patients; the peritubular uptake evident in normal subjects is not detectable. Urinary excretion and clearance of Cp remain significantly higher in IDDM patients. In both groups, renal uptake of C-peptide is directly related to its renal load: however, in IDDM, the increase in Cp uptake for each increment in renal load is 35% lower than in controls (p < 0.001). Furthermore, as opposed to controls, urinary Cp excretion is not correlated with its arterial levels. Therefore IDDM patients have marked defects in renal handling of endogenous Cp, regarding both the amount metabolized by renal tissue and that reabsorbed by tubular cells. These data indicate an early alteration in the diabetic kidney that also impairs the reliability of urinary Cp evaluation as an index of residual beta cell activity in IDDM patients.

Blood pressure and urinary C-peptide excretion in subjects with varying degrees of glucose tolerance.

To determine whether blood pressure is associated with 24-h urinary C-peptide excretion in subjects with varying degrees of glucose tolerance, we studied 247 Japanese men aged 30-69 who had never been treated with antihypertensive medications or with insulin. Plasma glucose and insulin responses during a 75-g oral glucose tolerance test, blood pressure and body mass index were obtained and urinary C-peptide excretion, in total and per kg body weight, were examined by 24-h urine collection. In monovariate analyses, urinary C-peptide excretion per kg body weight increased significantly as the blood pressure level rose (p < 0.05). After adjustment for age and body mass index by analysis of covariance, this relationship remained significant (p < 0.05), where adjusted mean values (+/- SEM) of urinary C-peptide per kg body weight were 1.56 +/- 0.05 microgram/24h/kg in the normotensive group and 2.04 +/- 0.17 microgram/24h/kg in the hypertensive (stage 2-4) group. When stratified simultaneously by glucose tolerance status and blood pressure level, adjusted mean values of urinary C-peptide per kg body weight were significantly higher in diabetic hypertensives than in diabetic normotensives. These results suggest that increase in 24-h urinary C-peptide excretion, i.e. 24-h insulin secretion, might contribute to an elevation of blood pressure both in normal and diabetic individuals.

Urine C-peptide and atherogenic risk factors in diabetes mellitus: relevance to "syndrome X".

The relation between the C-peptide concentration in twenty-four-hour urine specimens and atherogenic risk factors was investigated in 38 patients with noninsulin-dependent diabetes mellitus in an attempt to determine the significance of urine C-peptide in diagnosing "syndrome X," which is characterized by insulin resistance. Weak positive correlations between twenty-four-hour urine C-peptide concentration and body mass index, systolic blood pressure (BP), diastolic BP, serum total cholesterol, and serum triglyceride were detected. A weak negative correlation was also apparent between urine C-peptide and serum high-density lipoprotein (HDL). The body mass index and serum triglyceride of patients with urine C-peptide excretion of > 100 micrograms/day were significantly higher than those in patients with normal urine C-peptide excretion (< 100 micrograms/day) (P < 0.01 and P < 0.02, respectively). Systolic BP, diastolic BP, serum total cholesterol, and serum HDL did not differ significantly between the two groups of patients. Results indicate that twenty-four-hour urine C-peptide concentration is of significance in determining whether a patient has a tendency to insulin resistance but has only limited value as a quantitative measure of endogenous insulin secretion.

Insulin versus a combination of insulin and sulfonylurea in the treatment of NIDDM patients with secondary oral failure

Aim: Comparison of the effectiveness of combined therapy vs. an insulin regimen in NIDDM patients with secondary failure of oral hypoglycemic agents. Research design, patients and methods: 27 NIDDM patients were randomly allocated to Group A ( n = 14, insulin) and Group B ( n = 13, insulin and sulfonylurea) with crossover after 3 months. After the next 3 months a decision was made about the further treatment according to the metabolic control. The patients were then treated for another year with the more successful regimen. Metabolic control, residual β-cell secretory capacity, degree of peripheral insulin resistance (clamp) and insulin dose were followed during the whole study. Results: (median, interquartile range, in brackets; ∗, statistically significant difference at P < 0,05): the combined therapy was better then insulin alone in 2 3 of patients. Glycemic control was better (HbA 1c at 3 months: Group A = 7.9(1.1)% vs. Group B = 7.0(0.5)% ∗; HbA 1c at 6 months: Group A = 7.4(1.5)% vs. Group B = 8.1(1.5)%. Insulin dose was lower during the combined therapy in the first 3 months: Group A = 0.62(0.18) U/kg body weight vs. Group B = 0.39(0.16) U/kg body weight ∗. Combined treatment was associated with increased C-peptide excretion both fasting and postprandially. No significant differences in peripheral insulin resistance were noted between the two groups. The combined treatment remained successful even after one year. The two groups of patients with different effective treatment did not differ significantly in any of the observed parameters. Conclusions: the combined therapy was more effective than insulin alone. Its favourable effect persisted after treatment for a year. It seems better to start the treatment of the oral failure with combined therapy compared with insulin first and later followed by combined therapy. On the basis of the observed parameters it is impossible to determine in advance which kind of treatment is more suitable for the individual patient.

Hyperglycemia facilitates urinary excretion of C-peptide by increasing glomerular filtration rate in non-insulin-dependent diabetes mellitus

We have evaluated the feasibility of monitoring the 24-hour urinary excretion rate of C-peptide (U-CPR) as a measure of integrated β-cell function in patients with non-insulin-dependent diabetes mellitus (NIDDM). In 37 normoalbuminuric patients, U-CPR of 117.9 ± 9.1 μg/d (mean ± SEM) during the poorly controlled glycemic phase (fasting plasma glucose [FPG], 171 ± 7 mg/dL; hemoglobin A 1C [HbA 1c], 8.8% ± 0.4%) was significantly higher than the value of 83.3 ± 13.7 μg/d ( P < .001) during the well-controlled phase (FPG, 135. ± 6 mg/dL; HbA 1c, 7.0% ± 0.2%), although the plasma insulin response to meals was lower during the former phase (53.3 ± 6.3 μU/mL) versus the latter phase (65.7 ± 6.6, P < .005). Endogenous creatinine clearance (Ccr) was significantly elevated during the poorly controlled phase (105.4 ± 7.3 v 88.7 ± 4.7 mL/min, P < .005). In 26 microalbuminuric patients, the plasma insulin response was greater during good glycemic control, but U-CPR did not differ between the two phases. Ccr was comparable at two phases in this group (92.7 ± 7.4 v 91.1 ± 5.9 mL/min, NS). U-CPR correlated positively with Ccr in both groups ( r = .593, P < .001 in normoalbuminuria; r = .585, P < .001 in microalbuminuria). In addition, when biosynthetic human C-peptide was infused intravenously at an identical rate in two healthy subjects, resulting steady-state plasma levels of CPR were lower, and fractional U-CPR was higher during the moderately hyperglycemic phase versus the euglycemic phase. The calculated metabolic clearance rate (MCR) of C-peptide was found to be increased in the presence of hyperglycemia. These results suggest that hyperglycemia enhances U-CPR through an increase of glomerular filtration rate (GFR), and therefore U-CPR as an index of residual β-cell function in diabetes should be used cautiously.

Metabolic effects of alterations in meal frequency in hypercholesterolaemic individuals

It has been suggested that the metabolic consequences of a given diet may depend in part on the frequency with which meals are eaten. To investigate the effects of meal frequency on plasma lipid metabolism, 16 free-living hypercholesterolaemic men and women consumed their usual diet as 3 or 9 meals/day in random order for 4 weeks. Dietary macronutrient intake and body weight remained similar on the 2 regimens. Fasting plasma lipids were measured after 2, 3 and 4 weeks on each regimen and there were no significant differences in the fasting concentrations of plasma total, LDL, and HDL cholesterol, triglycerides, apolipoprotein A-I and B and the ratio of total:LDL and LDL:HDL cholesterol (HDL-C) on the two diets. The mean (± S.D.) fasting total cholesterol was 6.73 ± 0.74 and 6.81 ± 0.88 mmol/l on 3 and 9 meals/day, respectively and LDL-C was 4.77 ± 0.66 and 4.87 ± 0.78 mmol/l, respectively. There was also no significant variation in the response of plasma triglycerides or serum insulin to a high fat meal following a 3 week adaptation to regimens of 3 and 9 meals/day. Finally the 24 h urinary output of C-peptide was similar on each diet. The consumption of isoenergetic diets as 3 and 9 meals/day did not influence fasting plasma lipid levels, C-peptide excretion or the plasma triglyceride response to a high fat meal of a group of free living hypercholesterolaemic subjects.