Increment of C-peptide after glucagon injection determines the progressive nature of Japanese type 2 diabetes: a long-term follow-up study.

Type 2 diabetes (T2D) is characterized by a steady worsening of ß-cell dysfunction as the disease progresses. The objective of this study was to estimate the decline of insulin secretion in Japanese type 2 diabetic patients (T2D-patients) by glucagon injection over an observation period of more than 10 years. Thirty-three T2D-patients were followed for 10.4 ± 1.4 years. Fasting C-peptide immunoreactivity (FCPR), the 6 min value of CPR after glucagon injection (6MCPR), and the increment of CPR (ΔCPR) were measured at baseline and follow-up. FCPR, 6MCPR, ΔCPR were significantly lower at follow-up than at baseline (p<0.05, p<0.005, and p<0.0005, respectively). The annual change of ΔCPR was significantly (p<0.05) greater than the annual change of FCPR (-0.062 ± 0.076 ng/mL/year and -0.025 ± 0.067 ng/mL/year, respectively). In contrast, CPR-index (an index of ß-cell function) and SUIT-index (secretory units of islets in transplantation) calculated based on fasting blood samples were unaltered. The annual changes of FCPR, 6MCPR, and ΔCPR were negatively correlated with the FCPR, 6MCPR, and ΔCPR values at baseline, respectively. Duration of diabetes, BMI, diabetic retinopathy, and secondary sulfonylurea failure at baseline were not correlated with the annual changes of FCPR, 6MCPR, and ΔCPR. In conclusion, our longitudinal observations suggest that ß-cell function progressively declines in Japanese T2D-patients. The annual declines of ΔCPR were more prominent than the annual declines of FCPR. ΔCPR after glucagon injection may be more useful for estimating individual longitudinal insulin secretion than fasting blood samples.

Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea.

Increased carotid intima-media thickness (IMT) and increased serum levels of inflammatory markers, such as C-reactive protein (CRP), interleukin (IL)-6, and IL-18, are associated with an increased risk of cardiovascular and cerebrovascular diseases. The aim of this study was to evaluate whether carotid IMT, a useful marker for early atherosclerosis, is associated with these inflammatory markers in patients with obstructive sleep apnea (OSA). Carotid IMT was investigated with ultrasonography in 36 patients with OSA and 16 obese control subjects. Serum levels of CRP, IL-6, and IL-18 were measured at 5:00 A.M. Carotid IMT (p < 0.001) and serum levels of CRP (p < 0.003), IL-6 (p < 0.005), and IL-18 (p < 0.03) of patients with OSA were significantly higher than those of obese control subjects. Carotid IMT was significantly correlated with serum levels of CRP (r = 0.61, p = 0.0001), IL-6 (r = 0.41, p = 0.01), and IL-18 (r = 0.45, p = 0.005), duration of OSA-related hypoxia (r = 0.60, p = 0.0001), and severity of OSA (r = 0.50, p = 0.002). In addition, the primary factor influencing carotid IMT was duration of hypoxia during total sleep time (p = 0.036). These results suggest that OSA-related hypoxia and systemic inflammation might be associated with the progression of atherosclerosis and thus might increase the risks of cardiovascular and cerebrovascular morbidity in patients with OSA.

[Coronary risk factor management in primary practice in Shibuya, Tokyo].

OBJECTIVES: Many large-scale clinical trials have confirmed that coronary risk factors such as hypertension, hyperlipidemia and diabetes mellitus predict a higher incidence of cardiovascular events and that control of these risk factors reduces the incidence. However, the actual management of such risk factors and the resultant improvement of the cardiovascular events in primary practice remains unclear. The Heart Care Network Shibuya, a voluntary study group of regional primary physicians, surveyed the management of coronary risk factors and the clinical outcomes. METHODS: Behavioral patterns of the coronary risk factor was investigated in the management and resultant changes of the risk factors in 209 outpatients (mean age 65.6 +/- 11.2 years) with more than one of hypertension, hyperlipidemia, diabetes mellitus or prior myocardial infarction for 1 year. RESULTS: Prescriptions of anti-hypertensive (from 1.3 +/- 0.8 to 1.4 +/- 0.8 drugs per patient) and antihyperlipidemia drugs (from 0.70 +/- 0.4 to 0.73 +/- 0.4 drugs per patient) did not significantly increase. Patient education for diet (93% to 97%, p = 0.077), exercise (69% to 81%, p < 0.05) and nonsmoking (66% to 86%, p < 0.05) significantly increased after 1 year. Blood pressure decreased from 142 +/- 16/81 +/- 10 to 138 +/- 78/78 +/- 9 mmHg (p < 0.05), serum total cholesterol level decreased from 215 +/- 39 to 203 +/- 39 mg/dl (p < 0.05). As a result, more patients attained the treatment goals recommended in the guidelines by the Japanese Society of Hypertension (34.6% to 46.8%) and Japan Atherosclerosis Society (40.2% to 49.5%), respectively. However, none of blood hemoglobin A1c level, body mass index or smokers significantly changed. CONCLUSIONS: Regional practitioners attempted to control all coronary risk factors. Hypertension and hyperlipidemia, which are relatively more dependent on the medical management, improved. In contrast, diabetes mellitus, obesity or smoking, which require life style changes, did not improve. The main issue in the risk factor management is how physicians act rather than specific actions.