Postprandial serum C‐peptide value is the optimal index to identify patients with non‐obese type 2 diabetes who require multiple daily insulin injection: Analysis of C‐peptide values before and after short‐term intensive insulin therapy

Aims/Introduction

Type 2 diabetes is a progressive disease characterized by a yearly decline in insulin secretion; however, no definitive evidence exists showing the relationship between decreased insulin secretion and the need for insulin treatment. To determine the optimal insulin secretory index for identifying patients with non‐obese type 2 diabetes who require multiple daily insulin injection (MDI), we evaluated various serum C‐peptide immunoreactivity (CPR) values.

Materials and Methods

We near‐normalized blood glucose with intensive insulin therapy (IIT) over a 2‐week period in 291 patients with non‐obese type 2 diabetes, based on our treatment protocol. After improving hyperglycemia, we challenged with oral hypoglycemic agent (OHA), and according to the responsiveness to OHA, patients were classified into three therapy groups: OHA alone (n = 103), basal insulin plus OHA (basal insulin‐supported oral therapy [BOT]; n = 56) and MDI (n = 132). Glucagon‐loading CPR increment (ΔCPR), fasting CPR (FCPR), CPR 2 h after breakfast (CPR2h), the ratio of FCPR to FPG (CPI), CPI 2 h after breakfast (CPI2h) and secretory unit of islets in transplantation (SUIT) were submitted for the analyses. Receiver operating characteristic (ROC) and multiple logistic analyses for these CPR indices were carried out.

Results

Many CPR values were significantly lower in the MDI group compared with the OHA alone or BOT groups. ROC and multiple logistic analyses disclosed that post‐prandial CPR indices (CPR2h and CPI2h) were the most reliable CPR markers to identify patients requiring MDI.

Conclusions

Postprandial CPR level after breakfast is the most useful index for identifying patients with non‐obese type 2 diabetes who require MDI therapy.     

Physical activity and sports participation in children and adolescents with type 1 diabetes mellitus

Background and aimRegular physical activity is of great importance in the management of type 1 diabetes mellitus (T1DM). We investigate here the levels of moderate/vigorous physical activity (MVPA) and participation in sporting activity in a sample of children and adolescents with T1DM and analyse whether they differed from healthy subjects. The family variables associated with MVPA or sports participation and the influence of exercise on metabolic parameters are also explored.Methods and resultsIn this cross-sectional case control study, 138 children and adolescents with T1DM (of which 67 were boys, age 13.6 ± 4.1 years; duration of diabetes 6.1 ± 3.8 years) and 269 (of which 120 were boys) healthy controls were studied. Weekly levels of MVPA and sports participation were investigated using a questionnaire. Body mass index standard deviation score (BMI-SDS) values, plasma total cholesterol, serum triglycerides and the mean glycated haemoglobin (A1c) levels over the past year were assessed in T1DM subjects. MVPA scores in T1DM patients were lower than in controls (p = 0.0004). MVPA was higher in boys than in girls, both in diabetic and control subjects; T1DM girls were less frequently engaged in MVPA than control girls. MVPA scores were significantly and independently correlated with sex, age and diabetic status. Lower triglyceride levels and fewer subjects with poor metabolic control were found more among physically active patients (MVPA > 5 days/week) than in inactive patients (weekly MVPA = 0). Sports participation was lower in T1DM patients than in controls (p = 0.002) and was significantly and independently correlated with sex, father's education level and diabetic status. Triglyceride levels and the percentage of subjects with poor metabolic control were significantly lower in sports participants than in non-participants.ConclusionsChildren and adolescents with T1DM appeared to spend less time in physical activity than their non-diabetic peers. Regular physical activity was associated with better metabolic control and lipid profile. Adolescents, particularly the girls, tended to be less active. Further efforts should be made to motivate patients with type 1 diabetes.     

Physical activity is associated with lower arterial stiffness in normal‐weight postmenopausal women

The impact of physical exercise, as preventative measure, to control the progression of cardiovascular disease in midlife remains under investigation. We aimed to investigate the effect of different levels of intensity of physical activity on metabolic and vascular profile in healthy postmenopausal women. A total of 625 healthy postmenopausal women (mean age 57.7 ± 7.6 years) were evaluated using the short IPAQ questionnaire for quantification of physical activity. The energy expenditure was estimated in metabolic equivalent of energy (MET) hours per week. Pulse wave velocity (PWV) was measured as an index of arterial stiffness. Intima‐media thickness of both right and left common carotid artery, carotid bulb and internal carotid artery, and combined carotid IMT were also assessed by non‐invasive and well‐validated methods. Mean values of PWV decreased linearly with increasing intensity of physical activity (classes of physical activity: sedentary vs walking vs moderate vs vigorous activity: 9.07 ± 1.22 m/s vs 9.12 ± 1.72 m/s vs 8.47 ± 1.31m/s vs 7.94 ± 0.40 m/s, ANOVA P for linear trend .003). In non‐obese postmenopausal women, PWV values associated with: (a) the total number of METs (b‐coefficient = −0.261, P = .002) as well as with SBP; (b) or with the number of moderate METs (b‐coefficient = −0.192, P = .025) as well as with age and SBP. No significant associations were observed between the intensity of physical exercise and arterial stiffness in the overweight‐obese group. Physical activity is negatively associated with arterial stiffness in postmenopausal women with normal weight. This association was not observed in overweight or obese women.     

Parameters associated with residual insulin secretion during the first year of disease in children and adolescents with Type 1 diabetes mellitus

Factors associated with residual insulin secretion and spontaneous remission in Type 1 diabetic patients are important in the evaluation of treatment aimed at modifying the natural history of Type 1 DM. We investigated the effect of parameters at onset on residual beta cell function in 215 Type 1 DM children and adolescents. Blood gas analysis, HLA, GAD and IA-2 antibodies before the start of insulin treatment were recorded for each patient. Residual C-peptide secretion was assessed by the glucagon test, and parameters of metabolic control (HbA_1c and insulin dose U kg⁻¹ day⁻¹) were examined at disease onset and after 3, 6, and 12 months. Residual C-peptide secretion throughout the first year of disease was significantly reduced in patients with disease onset before age 5. Multiple regression analysis showed that low pH at onset showed a significant and independent association with reduced C-peptide at 3 months (p = 0.02) and that the detection of GAD antibodies had a significant independent association with decreased C-peptide secretion at 6 months of follow-up (p = 0.02). Insulin requirement was higher in the youngest patients group and in patients with GAD antibodies. Spontaneous insulin remission (HbA_1c <6 % and insulin <0.3 U kg⁻¹ day⁻¹) occurred in 22/192 (11 %) patients at 3 months of follow-up, in 15/190 (8 %) patients at 6 months and in 8/169 (5 %) patient at 12 months. Remission was more prevalent in older patients (p = 0.01) and in patients without detectable GAD antibodies: (14/64 vs 8/128, p = 0.001). Sex, IA-2 antibodies and HLA DR were not independently associated with C-peptide secretion, insulin requirement or remission in the first year of Type 1 DM. This study confirms the association of young age, severe acidosis at disease onset, and GAD antibodies with decreased residual beta-cell function and spontaneous remission during the first year of insulin treatment. These factors should be considered in trials evaluating therapies to retain beta-cell function and induce remission at and after disease onset. © 1998 John Wiley & Sons, Ltd.     

Shape of the glucose response curve during an oral glucose tolerance test is associated with insulin clearance and muscle insulin sensitivity in healthy non‐obese men

Individuals with a monophasic glucose response curve (GRC) during a 75‐g oral glucose tolerance test have a higher risk for type 2 diabetes than those with a biphasic GRC. However, no studies have addressed the association between GRC type and insulin clearance. Thus, we studied 49 healthy non‐obese Japanese men. We divided study participants into the monophasic or biphasic group based on the shape of their GRC. We evaluated tissue‐specific insulin sensitivity and insulin clearance using a two‐step hyperinsulinemic‐euglycemic clamp. The monophasic group had more visceral fat, lower insulin clearance and lower muscle insulin sensitivity than the biphasic group, whereas liver and adipose tissue insulin sensitivity, and insulin secretion were comparable. In conclusion, healthy non‐obese men with a monophasic GRC have lower insulin clearance and muscle insulin sensitivity.