ABSTRACT
OBJECTIVE Continuous beta-cell rest with diazoxide preserves residual endogenous insulin production in type 1 diabetes. However, side effects have hampered therapeutic usefulness. In a double-blind study, we tested whether lower, intermittent dosing of diazoxide had beneficial effects on insulin production, metabolic control, and autoimmunity markers in the absence of side effects. RESEARCH DESIGN AND METHODS Forty-one newly diagnosed type 1 diabetic patients were randomized to 6 months of treatment with placebo or 100 mg diazoxide at bedtime. A1C, C-peptide (fasting and glucagon stimulated), and FoxP3(+) regulatory T-cells (Tregs) were measured. Patients were followed for 6 months after intervention. RESULTS Of six dropouts, three were due to perceived side effects; one subject in the diazoxide group experienced rash, another dizziness, and one in the placebo group sleep disturbance. Adverse effects in others were absent. Diazoxide treatment reduced A1C from 8.6% at baseline to 6.0% at 6 months and 6.5% at 12 months. Corresponding A1C value in the placebo arm were 8.3, 7.3, and 7.5% (P < 0.05 for stronger reduction in the diazoxide group). Fasting and stimulated C-peptide decreased during 12 months similarly in both arms (mean -0.30 and -0.18 nmol/l in the diazoxide arm and -0.08 and -0.09 nmol/l in the placebo arm). The proportion of Tregs was similar in both arms and remained stable during intervention but was significantly lower compared with nondiabetic subjects. CONCLUSIONS Six months of low-dose diazoxide was without side effects and did not measurably affect insulin production but was associated with improved metabolic control.
Subject(s)
Autoimmunity/drug effects , Blood Glucose/drug effects , Diabetes Mellitus, Type 1/drug therapy , Diazoxide/administration & dosage , Insulin-Secreting Cells/drug effects , Adult , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Autoimmunity/physiology , Blood Glucose/metabolism , Body Weight/drug effects , Circadian Rhythm/physiology , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/physiopathology , Diazoxide/adverse effects , Diazoxide/pharmacology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Hypoglycemia/epidemiology , Insulin/administration & dosage , Insulin-Secreting Cells/physiology , Male , Placebos , Time FactorsABSTRACT
BACKGROUND: Patients with diabetes mellitus have an increased risk of colorectal cancer. However, there is limited information on the outcome for diabetic patients diagnosed with this type of cancer. METHODS: The health records of all 1 194 patients treated for colorectal adenocarcinoma at Levanger Hospital from 1980-2004 were reviewed. Diabetes status and prognostic factors were registered. Primary endpoints were cancer specific survival and overall survival. RESULTS: There were no significant differences between diabetic patients and non-diabetic patients concerning stage, grade, treatment, infective or non-infective postoperative complications, hospital stay, or 30 days mortality after laparotomy. After a curative resection, the estimated 5-year cancer specific survival in 97 diabetic patients was 73% (95% CI 60-87) and 79% (95% CI 75-82) in 1097 non-diabetic patients (not significant). The estimated overall 5-year survival in patients treated with curative intent was 46% (95% CI 33-59) in diabetic patients and 65% (95% CI 62-69) in non-diabetic patients (p<0.001). The diabetic patients were significantly older and more frequently had cardiac diseases. CONCLUSION: Diabetes mellitus did not affect the short-term survival or the cancer specific survival. A shorter overall survival was associated with cardiac diseases and higher age.
