Renal and splanchnic exchange of human biosynthetic C-peptide in Type 1 (insulin-dependent) diabetes mellitus

Summary Biosynthetic human C-peptide or NaCl (154 mmol·l^–1) was given intravenously to 13 Type 1 (insulin-dependent) diabetic patients to determine the renal and splanchnic exchange of C-peptide. Catheters were inserted percutaneously into an artery and a renal and hepatic vein. Infusions of C-peptide were given for 60 min at two dose levels (5 and 30 pmol·kg^–1·min^–1). Insulin was infused throughout the study (0.5 mU·kg^–1·min^–1) and plasma glucose was kept constant by a variable glucose infusion. The regional blood flows were measured by indicator dilution techniques. In 11 of the 13 patients basal C-peptide levels were not detectable. The arterial steady-state C-peptide concentration was 0.81±0.10 nmol·l^–1 and 2.33±0.30 nmol·l^–1 at the low and high rate infusions, respectively. Renal uptake was 124±18 pmol·min^–1 at the low infusion corresponding to 39% of the infused amount. At the higher dose C-peptide infusion renal uptake increased to 155±21 pmol·min^–1 (p<0.05). Urinary excretion of C-peptide was 7±2 pmol·min^–1 at the low dose infusion and increased to 34±6 pmol·min^–1 at the high dose infusion (p<0.01). The proportions of infused amount excreted were fairly constant and between 2% and 3%. No net exchange of C-peptide was found across the splanchnic vascular bed. The rate of glucose infusion had to be increased by 35% during the low dose C-peptide, but not during NaCl infusion in order to maintain a constant plasma glucose concentration. Arterial plasma concentrations of noradrenaline increased by 15–25% during both C-peptide and NaCl infusions. It is concluded that in patients with Type 1 diabetes (a) the kidney is the primary site of C-peptide removal, (b) renal metabolism rather than urinary excretion is the dominating process for C-peptide elimination (c) the excreted proportions of an infused amount of C-peptide were fairly constant between 2% and 3% and (d) no hepatic C-peptide catabolism could be detected.     

Residual insulin production,glycaemic control and prevalence of microvascular lesions and polyneuropathy in long-term Type 1 (insulin-dependent) diabetes mellitus

Summary The aim of the present study was to evaluate the role of residual insulin production in long-term Type 1 (insulin-dependent) diabetes mellitus. Ninety-seven patients with a disease duration of 9–16 years and onset before the age of 30 years were studied. C-peptide excretion in 24-h urine samples was measured as an indicator of residual insulin production. Thirty-five patients (36%) excreted C-peptide (>-0.2 nmol); as many as possible of them were carefully matched with a non-excretor patient with regard to age at onset of diabetes and disease duration. Twenty-nine pairs were obtained, and 22 of them agreed to participate in further investigations of glycaemic control and microangiopathic lesions. The patients who excreted C-peptide had significantly lower HbA_1c than the non-excretor group, 6.9±0.3% vs 7.9±0.3%, (p<0.025). Moderate-to-advanced background retinopathy was found in 2 patients in the excretor group and in 7 patients in the nonexcretor group. Microalbuminuria [ratio of albumin: creatinine (mg/l:mmol/l) >-5] was found in 1 and in 5 patients, respectively, while proteinuria [ratio of protein: creatinine (mg/l: mmol/l× 10) >-136] was found in 0 and in 4 patients, respectively. Microalbuminuria and/or proteinuria was found in 7 of the non-excretor group as compared to 1 in the excretor group (p=0.046). When all the variables were taken into account, microalbuminuria and/or proteinuria and/or moderate-to-advanced background retinopathy was found in 3 of the excretor group compared to 11 of the non-excretor group (p=0.022). Reduced sensory and motor nerve conduction velocities were common findings and occurred with the same frequency in the two groups. The data suggest that residual insulin production in long-term Type 1 diabetes is associated with a more satisfactory glycaemic control and a lower prevalence of early microangiopathic eye and kidney lesions.     

Seasonality of Type 1 (insulin-dependent) diabetes mellitus: values of C-peptide,insulin antibodies and haemoglobin A1c show evidence of a more rapid loss of insulin secretion in epidemic patients

Summary According to month of diagnosis, 165 children who developed Type 1 (insulin-dependent) diabetes mellitus at the age of 0–16.2 years (mean±SD, 7.6±4.1 years) could be divided into 69 patients diagnosed during peak seasons (epidemic cases) and 96 patients diagnosed during months of low incidence (non-epidemic cases). Seasonality of onset of symptoms and of diagnosis was observed in both sexes in all age groups. The patients diagnosed during peak seasons had shorter duration of symptoms (13.2±8.1 days) as compared to 22.9±10.3 days; p<0.001 in the patients diagnosed during months of low incidence. At diagnosis, 88.4% (61/69) of the epidemic group had ketonuria as compared to 71.9% (69/96); p<0.06 in the non-epidemic patients. The values of C-peptide, insulin antibodies, haemoglobin A_1c and HLA-DR phenotype frequencies in the 69 epidemic patients were compared with those of the 96 non-epidemic patients. In the epidemic patients, the C-peptide values of 0.11±0.05 mmol/l at diagnosis had increased to 0.12±0.05 mmol/l at one month and 0.13±0.06 mmol/l at 3 months. These values were significantly lower (p<0.001) than in the non-epidemic patients at the same time points: 0.17±0.08 nmol/l; p<0.001, 0.23±0.11 nmol/l; p<0.001, and 0.22±0.10 nmol/l. Values of insulin antibodies (U/l) of 0.06±0.03, 0.05±0.05 and 0.17±0.10 in the epidemic group compared to 0.014±0.015, 0.02±0.01, and 0.04±0.04 in the non-epidemic group at the same aforementioned time points also showed significant differences (p<0.001). Differences in these variables between the two groups continued until four years after diagnosis. Significant differences were also observed in the values of haemoglobin A_1c and HLA-DR phenotype frequencies in the two groups. The results suggest that children with Type 1 diabetes can be divided into two sub-groups with different early clinical course which might depend on a different aetiology, related both to seasonal variation at diagnosis and to a genetic heterogeneity.     

Erythrocyte 2,3-bisphosphoglycerate concentrations and haemoglobin glycosylation in normoxic Type 1 (insulin-dependent) diabetes mellitus

Summary Increased erythrocyte 2,3-bisphosphoglycerate concentrations are associated with increased haemoglobin glycosylation in patients with Type 1 diabetes mellitus who have no cause or symptoms of hypoxic stress. This change in 2,3-bisphosphoglycerate metabolism is additional to its response to changes in circulating haemoglobin concentration. Statistical analysis of data showed that erythrocyte 2,3-bisphosphoglycerate concentration did not correlate with the absolute concentration of circulating haemoglobin A_1c, but with the proportion of haemoglobin glycosylated. This finding is consistent with the hypothesis that it is changes in the position of the erythrocyte oxygen dissociation curve which modulate the increase in 2,3-bisphosphoglycerate synthesis upon haemoglobin A_1c formation.     

Glycosylated haemoglobin and steady-state mean blood glucose concentration in type 1 (insulin-dependent) diabetes

Summary Since glucose control and glycosylated haemoglobin varies asyncroneously, we have studied the steady-state relationship between these two factors. In Type 1 (insulin-dependent) diabetic patients with a constant haemoglobin A_1c during the preceding 2 years, 15 ambulatory blood glucose profiles during a 5-week period showed a constant glucose level and provided a precise estimate of the mean blood glucose concentration. In addition, we studied 15 non-diabetic subjects who provided three glucose profiles and had one haemoglobin A_1c determination performed. A good correlation was found for a curvilinear relationship (haemoglobin A_1c=2.07 x mean blood glucose^0.596, r=0.98). This close relationship indicates that glycosylated haemoglobin is a valuable, but not very sensitive, index of glucose control.     

Improvements in cognition, mood and behaviour following commencement of continuous subcutaneous insulin infusion therapy in children with type 1 diabetes mellitus: a pilot study

Aims/hypothesis  Anecdotally, parents and teachers of children with type 1 diabetes mellitus report improvements in behaviour and learning following the commencement of continuous subcutaneous insulin infusion (CSII). This study aimed to investigate changes in cognition, mood and behaviour following commencement of CSII in children with type 1 diabetes. Methods  Children (n = 32) with type 1 diabetes aged 6–16 years and starting CSII at two Australian centres underwent behavioural, cognitive and glycaemic assessments prior to the commencement of CSII and 6–8 weeks after its start. A comprehensive cognitive test battery was administered, comprising measures of intelligence, attention, processing speed and executive skills. Behaviour and mood were assessed using the Behaviour Assessment System for Children—Second Edition. Continuous glucose monitoring was performed over a 72 h period and HbA_1c was measured at both time-points. Results  After commencement of CSII, there were significant improvements in HbA_1c, a reduction in hyperglycaemia and blood glucose variation and an increase in normoglycaemia. Significant improvements were observed in perceptual reasoning, selective attention, divided attention, cognitive flexibility and working memory. Fewer mood-related symptoms were reported (parent, teacher and self-report) and fewer behavioural problems (parent reports) Conclusions/interpretation  In this uncontrolled pilot study, children with type 1 diabetes demonstrated significant improvements in measures of metabolic control, mood and behaviour and in some complex cognitive skills after commencing CSII therapy.     

Fasting plasma C-peptide,glucagon stimulated plasma C-peptide,and urinary C-peptide in relation to clinical type of diabetes

Summary Many patients with Type 2 (non-insulin-dependent) diabetes mellitus are treated with insulin in order to control hyperglycaemia. We studied fasting plasma C-peptide, glucagon stimulated plasma C-peptide, and 24 h urinary C-peptide in relation to clinical type of diabetes in 132 insulin treated diabetic subjects. Patients were classified clinically as Type 1 (insulin-dependent) diabetic subjects in the presence of at least two of the following criteria: 1) significant ketonuria, 2) insulin treatment started within one year after diagnosis, 3) age of diagnosis 40 years, and 4) weight below 110% of ideal weight of the same age and sex. Eighty patients were classified as Type 1 and 52 as Type 2 diabetic subjects. A second classification of patients into 6 C-peptide classes was then performed. Class I consisted of patients without islet B-cell function. Class II-VI had preserved islet B-cell function and were separated according to the 20%, 40%, 60% and 80% C-peptide percentiles. The two classifications of patients were compared by calculating the prevalence of clinical Type 1 and Type 2 diabetes in each of the C-peptide classes. This analysis showed that patients with a fasting plasma C-peptide value <0.20 nmol/l, a glucagon stimulated plasma C-peptide value <0.32 nmol/l, and a urinary C-peptide value <3.1 nmol/l, or <0.54 nmol/mmol creatinine/24 h, or <5.4 nmol/24 h mainly were Type 1 diabetic patients; while patients with C-peptide levels above these values mainly were Type 2. At these limits the percentage, predictive value of positive tests as indicators of Type 2 diabetes were as follows: fasting C-peptide 83%, stimulated C-peptide 86%, and urinary C-peptide expressed as nmol/l 76%, as nmol/mmol creatinine/24 h 79%, and as nmol/24 h 78%. Similarly, the percentage predictive value of negative tests as indicators of Type 1 diabetes were as follows: fasting C-peptide 86%, stimulated C-peptide 88%, and urinary C-peptide expressed as nmol/l 79%, as nmol· mmol creatinine·24 h 81%, and as nmol/24 h 80%. If patients without detectable C-peptide were excluded, the predictive value of negative tests were as follows: fasting C-peptide 81%, stimulated C-peptide 88%, urinary C-peptide expressed as nmol/l 61%, as nmol/mmol creatinine/24 h 69%, and as nmol/24 h 64%. In conclusion, post glucagon C-peptide gives a good distinction between Type 1 and Type 2 diabetes mellitus in insulin treated diabetes while 24 h urinary C-peptide gives a less sensitive distinction between the clinical types of diabetes.     

Proinsulin and C-peptide at onset and during 12 months cyclosporin treatment of Type 1 (insulin-dependent) diabetes mellitus

Summary An increased proinsulin to C-peptide molar ratio at the onset of Type 1 (insulin-dependent) diabetes mellitus has been suggested. We studied fasting proinsulin levels and proinsulin/C-peptide ratios in the newly diagnosed diabetic subjects participating in the Canadian/European placebo controlled cyclosporin study at entry, during the one year treatment period and six months of follow-up. Available entry data from 176 out of the 188 allocated patients were compared to 60 age and weight matched control subjects. Fasting proinsulin was significantly elevated in male patients compared to male control subjects (p<0.01), whereas the levels only tended to be elevated in female patients. The proinsulin/C-peptide ratio was three to fourfold elevated in the diabetic groups of both sexes, (p<0.001). Further, proinsulin and C-peptide were studied in 83 cyclosporin and 86 placebo-treated subjects during the trial and follow-up. An additional increase of proinsulin/C-peptide ratio was observed during the first three months of placebo treatment. It remained constantly high for nine months and then declined to entry level. This pattern was not seen in the cyclosporintreated group, where the ratio was unchanged during the 12 months trial and follow-up. The effect of cyclosporin on the induction of non-insulin requiring remission was unrelated to fasting and glucagon stimulated C-peptide levels at entry, whereas 64% of the cyclosporin-treated against 28% of the placebo-treated subjects (p<0.01) went into remission if the proinsulin/C-peptide ratio at entry was above 0.024. If the ratio was below 0.024 at entry, 42% and 33% went into non-insulin requiring remission, respectively (NS). We conclude that fasting proinsulin to C-peptide molar ratio is elevated at the onset of Type 1 diabetes mellitus. A further plateaushape elevation lasting nine months was seen during the remission period. Cyclosporin seems to inhibit or delay this development. The proinsulin/C-peptide ratio at diagnosis may show to be of value in the prediction of remission during cyclosporin treatment.Prepared by the authors for The Canadian/European Diabetes Study Group.     

Twenty-four hour profiles of plasma C-peptide in Type 1 (insulin-dependent) diabetic children

Summary Twenty-four hour profiles of plasma C-peptide an index of endogenous insulin secretion, were performed in 15 Type 1 (insulin-dependent) diabetic children. Plasma C-peptide was detectable in six children, of whom four (C-peptide producers) had peak values above normal fasting levels. In each of the six children with residual B cell function, there was a close correlation between plasma C-peptide and simultaneous blood glucose (r> 0.50, p< 0.05). Post-breakfast peak blood glucose was 10.2 ± 1.7 mmol/l (mean ±SEM) in the C-peptide producers and 18.7 ± 1.7 mmol/l in the 11 children with low or no detectable C-peptide. Mean M-value, an index of deviation from an ideal blood glucose, was lower in the C-peptide producers (p<0.05). It is concluded that residual functioning B cells in diabetic children behave physiologically in that insulin secretion fluctuates in accordance with the prevailing blood glucose; and that the pattern of action of injected insulin is more critical in non-C-peptide producers who lack the post-prandial dampening effect provided by residual endogenous insulin secretion.     

C-peptide measurement in the differentiation of Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus

Summary To determine whether individual subjects with Type 1 (insulin-dependent) diabetes or Type 2 (non-insulin-dependent) diabetes, who are treated with insulin, could be reliably distinguished, C-peptide concentrations and urinary C-peptide excretion were measured in 10 Caucasoids and 10 Pima Indians. All the subjects had developed diabetes before 21 years of age and were receiving insulin treatment. Fasting C-peptide concentrations were significantly higher in the Pima Indians (0.73±0.17 versus 0.02±0.01 nmol/l in Caucasoids; p<0.001), but there were slight overlaps in individual values. Urinary C-peptide excretion, an index of 24-h-insulin excretion, was also higher in the Pima Indian group (27.6±1.85 versus 0.72±0.18 pmol/min in Caucasoids; p<0.001) and there was no overlap in the individual values between the groups. The Pima Indians with early onset diabetes have been previously shown to have Type 2 diabetes, and the Caucasoids with an early onset are most likely to have Type 1 diabetes. These results suggest that distinction between these two major types of diabetes can be made effectively by using C-peptide measurements provided that overt renal disease is absent. This differentiation between insulin-treated patients will be useful for a variety of research applications and possibly in making clinical management decisions.     

Diabetic control in 102 insulin-treated out-patients

Summary Haemoglobin A_1c concentrations were measured in 102 insulin-treated diabetic outpatients. Only 19% had Hb A_1c levels below three standard deviations above the normal mean value (5.23±0.05%). There were no correlations between Hb A_1c levels, random C-peptide immunoreactivity or age. A significant correlation (r = 0.49; p< 0.001) was, however, observed between HbA_1c and random plasma glucose levels. The mean random plasma glucose value was normal (89±18 mg/ 100 ml; 5±1 mmol/l) in the patients on insulin three times a day who had received short acting insulin 160 ±6 min before the sampling. — A significant inverse correlation was found (r = -0.26; p<0.01) between the number of daily insulin injections and the HbA_1c concentration. — These results suggest that the use of multiple daily insulin injections improves diabetic control. It should however be emphasised that the patients receiving multiple insulin injections were younger than those on the single injection regime and had lower plasma insulin antibody titres, different social and psychological status and a shorter duration of the disease.     

Residual B cell function in diabetic children as determined by urinary C-peptide

Summary C-peptide was determined in 24-h urine collections and in fasting plasma of 27 Type 1 (insulin-dependent) diabetic children (duration of disease 0–6 years) and in 11 matched normal children. Grouping the patients according to duration of disease from onset to 6 years, it was found that in the first year of disease the B cell reserve was a mean of 4.89±1.95 pmol · mg creatinine^-1. 24 h^-1 compared with a mean of 24.51±2.91 pmol · mg^-1 · 24 h^-1 in the control group. A further diminution was seen with increase in the duration of disease, until after 6 years when only traces of C-peptide could be detected. There was a good correlation between the levels of plasma C-peptide and urinary C-peptide values as related to creatinine (r = 0.89; p = < 0.001). In view of this, and since it is simpler and less traumatic to obtain frequent urine samples from children than it is to obtain blood samples, it was felt that the determination of urinary C-peptide constitutes a valuable tool in the evaluation of the diabetic child.     

Continuous Glucose Monitoring System in children with type 1 diabetes mellitus: a systematic review and meta-analysis

Aims/hypothesis We investigated the potential effects of the Continuous Glucose Monitoring System (CGMS), as compared with self-monitoring of blood glucose, on glycaemic control in children with type 1 diabetes. Methods The following electronic databases were searched throughout June 2007: MEDLINE, EMBASE and The Cochrane Library. Additional references were obtained from reviewed articles. Only randomised controlled trials were included. Results We included five trials involving 131 type 1 diabetic patients in the study. Combined data from all trials showed that the CGMS did not significantly reduce HbA_1c levels compared with control groups. The pooled weighted mean difference was −0.02% (95% CI −0.29 to 0.25) with a fixed model and remained insignificant in the random effect model. Sensitivity analysis determined that the findings were stable. There was a trend towards a longer time under the CGMS curve for glucose <3.89 mmol/l in the CGMS group compared with the control group (mean difference 49.00 min, 95% CI −18.00 to 116.00). The CGMS significantly increased the number of insulin dose changes per patient per month for those managed with CGMS compared with the control groups (mean difference 6.3 changes, 95% CI 2.88–9.72). Conclusions/interpretation The Continuous Glucose Monitoring System is not better than self-monitoring of blood glucose with regard to improvement of metabolic control among type 1 diabetic children. However, due to the small number of participants and methodological limitations of the studies included, findings of this meta-analysis should be interpreted with caution. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Islet cell antibodies and fasting C-peptide predict insulin requirement at diagnosis of diabetes mellitus

Summary The differential diagnosis between Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes is complicated since no specific markers are available for either disease. In this study, 244 consecutive patients were diagnosed with diabetes mellitus during two years in Malmö (230000 inhabitants), corresponding to an incidence rate of 53·100000^–1·year^–1. Age, body mass index, HbA_1c, C-peptide, and levels of islet cell antibodies were determined at the clinical onset, and related to the classification at diagnosis and at follow-up (n=233) after a median time of 31 (range 1–49) months. After diagnosis, 42 of 244 (17%) were started on insulin while 202 of 244 (83%) were not. Islet cell antibodies were present in 25 of 42 (60%), and in 18 of 183 (10%), respectively. In the non-insulin treated group, patients with islet cell antibodies had lower body mass index (p<0.001), higher HbA_1c (p<0.004), and lower C-peptide (p<0.001) than patients without. At follow-up, 11 of 18 (61%) islet cell positive patients were changed to insulin treatment, as were six other patients. Insulin was discontinued in five initially insulin-treated but islet cell antibody negative patients. The sensitivity, specificity and predictive value for insulin treatment at follow-up were for islet cell antibody positivity; 72%, 96% and 84%, respectively, and for low C-peptide value; 60%, 96%, and 80%, respectively. Islet cell antibodies and low C-peptide at diagnosis of diabetes mellitus are concluded to be useful markers to predict insulin dependence.     

Plasma lipids and lipoproteins in young insulin-dependent diabetic patients: Relationship with control

Summary Plasma and lipoprotein cholesterol and triglycerides, glucose and haemoglobin A_1c concentrations were measured in 106 patients (56 males) with insulin-dependent diabetes mellitus (age range 2–22 years) and 36 normal volunteers (19 males) with similar age and sex distribution. The diabetic patients were further divided into three subgroups: good, fair and poor control, based on 24 h glycosuria and haemoglobin A_1c concentrations. Total, low density lipoprotein and very low density lipoprotein cholesterol levels were significantly increased in male patients in poor control when compared with the group in good control and with normal subjects. Triglyceride and very low density lipoprotein triglyceride levels were also significantly increased in poorly controlled males. The most significant difference however was a decrease of high density lipoprotein cholesterol in male patients in poor control. There was a significant inverse correlation between haemoglobin A_1c and high density lipoprotein cholesterol (r = -0.63) and a direct correlation between haemoglobin A_1c and low density lipoprotein cholesterol (r = 0.35) and triglycerides (r = 0.62) in the male diabetics. The findings were similar in females. The most striking change was observed in low density lipoprotein cholesterol levels, which were more markedly increased in poorly controlled females than in poorly controlled males. No statistical singificant differences were found between the groups in good and fair control for any of the plasma and lipoprotein lipids studied. A significant difference however was found between the groups in poor and fair control. There was a significant correlation in females between haemoglobin A_1c and low density lipoprotein cholesterol levels (r = 0.43), haemoglobin A_1c and triglycerides levels (r = 0.54) and an inverse correlation between haemoglobin A_1c and high density lipoprotein cholesterol (r = -0.59).     

Increased reduction in fasting C-peptide is associated with islet cell antibodies in Type 1 (insulin-dependent) diabetic patients

Summary A cohort of 82 patients with Type 1 (insulin-dependent) diabetes was followed prospectively for 24 months, and 54 of them for 30 months, to study the relationship between fasting levels of immunoreactive C-peptide and titres of islet cell antibodies. After diagnosis, fasting C-peptide rose temporarily for 1–6 months of insulin therapy and declined continuously thereafter. While islet cell antibodies were present among 55% of the newly diagnosed patients, only 31% remained positive at 30 months. Their antibody titres decreased from 181 at diagnosis to 13. Only 3 patients (4%) who were islet cell antibody negative at diagnosis became positive later. The median C-peptide values among the persistently islet cell antibody positive patients decreased from 0.11 pmol/ml at 18 months, to 0.09 pmol/ml at 24 months, to 0.06 pmol/ml at 30 months compared to 0.18 (p=0.04), 0.15 (p=0.05) and 0.16 (p< 0.003) pmol/ml, respectively, for the islet cell antibody negative patients. The median slope for the latter was –0.09 compared to –0.19 for the islet cell antibody positive patients (p=0.01). These differences were reflected in increasing dosages of insulin, since patients remaining antibody-positive for 30 months were given 1.3–1.4 times more insulin (p=0.01–0.004) than the antibody negative patients. This study demonstrates that islet cell antibodies may be a useful marker for predicting an increased rate by which endogenous B cell function is lost in Type 1 diabetes.     

Improved metabolic control does not alter the charge-dependent glomerular filtration of albumin in uncomplicated Type 1 (insulin-dependent) diabetes

Summary The selectivity index, i. e. clearance of non glycated albumin/clearance of glycated albumin was studied in fourteen patients with Type 1 (insulin-dependent) diabetes and normal urinary albumin excretion. The index was increased above one in all patients, and correlated significantly to HbA_1c. It was, however, unaffected by 12 weeks of improved metabolic control with a mean decline in HbA_1c of 1.9% in seven patients. We conclude that the increased electronegative charge of the glomerular filtration barrier observed in uncomplicated diabetes is related to long term metabolic control but not reversible during twelve weeks of strict metabolic control. This indicates a slow turnover of the components responsible for the increased charge selectivity in uncomplicated diabetes.     

C-peptide concentrations in patients with type 2 diabetes treated with insulin

AimsTo determine beta cell reserves of patients with type 2 diabetes who are treated with insulin by using fasting C-peptide concentrations and to investigate the clinical features related to C-peptide concentrations.Materials and methodsPatients with type 2 diabetes, who were using insulin as monotherapy or in combination therapy, were divided into three groups; those with an insufficient beta cell reserve (C-peptide: <0.5 ng/mL), borderline reserve (C-peptide: 0.5–2 ng/mL) and sufficient reserve (C-peptide:> 2 ng/mL).ResultsIn the 249 patients (mean age, 61.77 ± 9.34 years; 40.6% male), the mean duration of diabetes was 13.9 ± 8.43 years. The mean HbA1c concentrations, fasting glucose and C-peptide concentrations were 8.88 ± 1.87%, 184.29 ± 77.88 mg/dL and 1.95 ± 1.37 ng/mL, respectively. Fifty-seven percent of patients (n = 142) had a borderline beta cell reserve and 37% (n = 92) had high C-peptide concentrations. Only 6% of patients (n = 15) had an insufficient beta cell reserve. C-peptide levels were positively correlated with waist circumference (r: 0.282; p = 0.001), hip circumference (r: 0.251; p = 0.001), body mass index (r: 0.279; p = 0.001), fasting glucose concentrations (r: 0.309; p = 0.001) and triglyceride concentrations (r: 0.358; p = 0.001).ConclusionIn this study, almost all patients with type 2 diabetes using insulin were found to have sufficient or borderline beta cell reserves and insulin resistance-related parameters were prominent in those with adequate beta cell reserve.Clinical trials noNCT04005261     

Early and late C-peptide responses during oral glucose tolerance testing are oppositely predictive of type 1 diabetes in autoantibody-positive individuals

We examined whether the timing of the C-peptide response during an oral glucose tolerance test (OGTT) in relatives of patients with type 1 diabetes (T1D) is predictive of disease onset. We examined baseline 2-h OGTTs from 670 relatives participating in the Diabetes Prevention Trial-Type 1 (age: 13.8 ± 9.6 years; body mass index z-score: 0.3 ± 1.1; 56% male) using univariate regression models. T1D risk increased with lower early C-peptide responses (30–0 min) (χ² = 28.8, P < 0.001), and higher late C-peptide responses (120–60 min) (χ² = 23.3, P < 0.001). When both responses were included in a proportional hazards model, they remained independently and oppositely associated with T1D, with a stronger overall association for the combined model than either response alone (χ² = 41.1; P < 0.001). Using receiver operating characteristic curve analysis, the combined early and late C-peptide response was more accurately predictive of T1D than area under the curve C-peptide (P = 0.005). Our findings demonstrate that lower early and higher late C-peptide responses serve as indicators of increased T1D risk.     

C-peptide levels in transient neonatal diabetes

A baby boy with transient neonatal diabetes mellitus presenting with hyperglycaemia, glycosuria, and dehydration without ketonuria on the second day of life is reported. C-peptide levels were measured to aid in the assessment of insulin treatment. Very low levels were found for the first 5 months of life (less than 0.06 nmol/l). Thereafter insulin treatment was discontinued and the baby thrived showing normal growth and development at age 2 1/2 years.