Use of the continuous glucose monitoring system to treat insulin autoimmune syndrome: quantification of glucose excursions and evaluation of treatment efficacy.

BACKGROUND: Autoimmune hypoglycaemia, based on the presence of autoantibodies directed against endogenous insulin (insulin autoimmune syndrome or Hirata's disease), is a rare cause of hypoglycaemia. Treatment of the disease is not standardized and various therapeutic options have been proposed. We wondered whether using a continuous glucose-monitoring system could help quantify precisely glucose excursions and allow evaluation of treatment efficacy. CASE REPORT: A 44-year-old Caucasian patient with insulin autoimmune syndrome was studied for 7 days using a continuous glucose monitoring system under various treatment regimens, i.e. diet modification, high-dose corticosteroids, alpha-glucosidase inhibitors, and plasmapheresis. CONCLUSION: Continuous glucose monitoring system data confirmed that insulin autoimmune syndrome alternated between periods of prandial hyperglycaemia and interprandial hypoglycaemia. Alpha glucosidase inhibitors and plasmapheresis were more potent in limiting glucose excursions than corticosteroid or diet-only treatments. The continuous glucose monitoring system appears to be a useful tool in the management of insulin autoimmune syndrome.

Six-year follow-up of a cohort of 203 patients with diabetes after screening for silent myocardial ischaemia.

AIMS: To determine the prognosis of patients with Type 1 or Type 2 diabetes, 6 years after screening for silent myocardial ischaemia (SMI). METHODS: Two hundred and three asymptomatic patients with diabetes underwent systematic SMI screening. From the results of this screening, they were allocated to one of three groups: patients (n = 171) with negative screening; patients (n = 32) with positive screening; and patients (n = 21) with positive screening and coronary stenosis. Six years after the initial assessment, all patients were re-assessed. All events [death, cardiac death, non-fatal major cardiac events (NFMCEs)--acute myocardial infarction, ventricular rhythm disorders, heart failure, unstable angina] were recorded. RESULTS: Fifteen patients were lost to follow-up. Patients (n = 20) with positive SMI screening and coronary stenosis had a higher risk of NFMCEs (35% vs. 7%, P < 0.001), and a higher mortality rate (35% vs. 15%, P < 0.05) compared with patients (n = 157) with negative screening. SMI-positive patients (n = 31) had a higher NFMCE rate compared with negative SMI screening patients, although overall mortality rate was no different. Cancer was the leading cause of death (36.4%). In multivariate analysis, major cardiac events (cardiac death and NFMCE) were related to baseline age, body mass index and coronary stenosis (P < 0.01). CONCLUSIONS: Patients with diabetes and SMI have a very poor prognosis as assessed by cardiac events or death, especially in the presence of coronary stenosis.

Acute hyperinsulinism modulates plasma apolipoprotein B-48 triglyceride-rich lipoproteins in healthy subjects during the postprandial period.

The role of postprandial insulin in the regulation of postprandial lipid metabolism is still poorly understood. The roles of hyperinsulinemia and insulin resistance in the alteration of postprandial lipid metabolism are not clear either. To improve knowledge in this area, we submitted healthy men to acute hyperinsulinemia in two different ways. In the first study, we compared in 10 men the effects of four isolipidic test meals that induce different degrees of hyperinsulinemia on postprandial lipid metabolism. Three different carbohydrate sources were compared according to their glycemic indexes (GIs; 35, 75, and 100 for white kidney bean, spaghetti, and white bread test meals, respectively); the fourth test meal did not contain any carbohydrates. Postprandial plasma insulin levels were proportional to the GIs (maximal plasma insulin concentrations: 113 +/- 16 to 266 +/- 36 pmol/l). We found a strong positive correlation during the 6-h postprandial period between apolipoprotein (apo) B-48 plasma concentration and insulin plasma concentration (r2 = 0.70; P = 0.0001). In a second study, 5 of the 10 subjects again ingested the carbohydrate-free meal, but during a 3-h hyperinsulinemic- (550 +/- 145 pmol/l plasma insulin) euglycemic (5.5 +/- 0.8 mmol/l plasma glucose) clamp. A biphasic response was observed with markedly reduced levels of plasma apoB-48 during insulin infusion, followed by a late accumulation of plasma apoB-48 and triglycerides. Overall, the data obtained showed that portal and peripheral hyperinsulinism delays and exacerbates postprandial accumulation of intestinally derived chylomicrons in plasma and thus is involved in the regulation of apoB-48-triglyceride-rich lipoprotein metabolism, in the absence of insulin-resistance syndrome.

[Effect of weight loss on adipose tissue distribution and insulin sensitivity].

OBJECTIVE: To discuss the effect of weight reduction on fat distribution and parameters of insulin sensitivity. METHODS: 12 Caucasian women with simple obesity, aged 21 to 65 years, were treated by low caloric and high protein diet for four weeks. A series of examinations were taken before and after the treat, using computerized tomography for visceral and subcutaneous fat, using euglycemic insulin clamp for parameters of insulin sensitivity. RESULTS: Weight loss was (6 +/- 2) kg (2-11 kg). body mass index (BMI), waist, total fat, visceral fat, and subcutaneous fat reduced significantly. However waist-hip rate, visceral-total fat rate, and subcutaneous-total fat rate did not change significantly. Fasting serum insulin, and fasting insulin-glucose rate decreased significantly. Insulin metabolic clearance rate and, insulin sensitive index increased significantly. Fasting peptide C did not change significantly. CONCLUSIONS: The low caloric and high protein diet can reduce visceral and subcutaneous fat. Weight loss can improve insulin sensitivity and increase insulin metabolic clearance rate.

Silent myocardial ischemia in patients with diabetes: who to screen.

OBJECTIVE: Silent myocardial ischemia (SMI) is more common in diabetic patients than in the general population. However, the exact prevalence of SMI is not known, and routine screening is costly. The purpose of this 1-year study was to estimate the prevalence of SMI and define a high-risk diabetic population by systematically testing patients with no symptoms of coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: The criteria for inclusion in this study were age (between 25 and 75 years), duration of diabetes (>15 years for type 1 diabetes, 10 years for type 2 diabetes with no cardiovascular risk factors, and 5 years for type 2 diabetes with at least one cardiovascular risk factor), and absence of clinical or electrocardiogram (ECG) symptoms of CAD. For 1 year, 203 patients were screened, including 28 women and 45 men with type 1 diabetes (aged 41.5+/-10.9 years, mean duration of diabetes 20.9+/-7.7 years [mean +/- SD]) and 61 women and 69 men with type 2 diabetes (aged 60.7+/-8.7 years, duration of diabetes 16.5+/-7.1 years). Exercise ECG was the first choice for screening method. If exercise ECG was not possible or inconclusive, thallium myocardial scintigraphy (TMS) with exercise testing and/or dipyridamole injection was performed. If any one of these tests was positive, coronary angiography was carried out and was considered to be positive with a stenosis of > or =50%. RESULTS: Positive screening results were obtained in 32 patients (15.7%). Coronary angiography demonstrated significant lesions in 19 patients (9.3%) and nonsignificant lesions in 7 patients (1 false-positive result for exercise ECG and 6 false-positive results for TMS). Coronary angiography was not performed in six patients. All but 3 of the 19 patients (15 men and 4 women) in whom silent coronary lesions were detected presented with type 2 diabetes. The main differences between the 16 type 2 diabetic patients presenting with coronary lesions and the type 2 diabetic patients without SMI were a higher prevalence of peripheral macroangiopathy (56.2 vs. 15.1%, respectively, P < 0.01) and a higher prevalence of retinopathy (P < 0.05). No correlation was found between SMI and duration of diabetes, HbA1c level, renal status, or cardiovascular risk factors except for family history of CAD. CONCLUSIONS: The results of this study allowed us to determine a high-risk group for SMI in the diabetic population. SMI with significant lesions occurs in 20.9% of type 2 diabetic male patients who are totally asymptomatic for CAD. Based on these findings, we recommend routine screening for male patients in whom the duration of type 2 diabetes is >10 years or even less when more than one cardiovascular risk factor is present.

Painful swelling of the thigh in a diabetic patient: diabetic muscle infarction.

A 44-year-old woman with a 5-year history of poorly controlled Type 1 diabetes mellitus presented with a painful, firm and warm swelling in her right thigh. Pain was severe but the patient was not febrile, and had no history of trauma or abnormal exercise. Laboratory tests showed ketoacidosis, major inflammation (erythrocyte sedimentation rate (ESR) = 83 mm/h), normal white blood cell count and normal creatine kinase level. Plain radiographs were normal, and there were no signs of thrombophlebitis at Doppler ultrasound. Magnetic resonance imaging (MRI) showed diffuse enlargement and an oedematous pattern of the adductors, vastus medialis, vastus intermedius and sartorius of the right thigh. The patient's symptoms improved dramatically, making biopsy unnecessary, and a diagnosis of diabetic muscular infarction was reached. Idiopathic muscular infarction is a rare and specific complication of diabetes mellitus, typically presenting as a severely painful mass in a lower limb, with high ESR. The diabetes involved is generally poorly controlled longstanding Type 1 diabetes with established microangiopathy. Differential diagnoses include deep vein thrombosis, acute exertional compartment syndrome, muscle rupture, soft tissue abscess, haematoma, sarcoma, inflammatory or calcifying myositis and pyomyositis. In fact, physician awareness should allow early diagnosis on the basis of clinical presentation, routine laboratory tests and MRI, thereby avoiding biopsy and its potential complications as well as unnecessary investigations. Rest, symptomatic pain relief and adequate control of diabetes usually ensure progressive total recovery within a few weeks. Recurrences may occur in the same or contralateral limb.

Visceral fat as a main determinant of plasminogen activator inhibitor 1 level in women.

OBJECTIVE: To substantiate in a premenopausal population of women, the link between visceral adipose tissue and circulating plasminogen activator inhibitor 1 (PAI-1) levels. DESIGN: Study of correlations between anthropometric parameters and PAI-1 and evaluation of the changes induced by weight loss. SUBJECTS: Forty-two healthy pre-menopausal women (aged 18-51 y, with a wide range of body mass index (BMI, 21-48.8 kg/m2). Thirteen women were evaluated after weight loss (6.6+/-3.3 kg). MEASUREMENTS: BMI, waist and hip circumferences. Total, subcutaneous and visceral adipose tissue areas at the L3-L4 level by computed tomography. Insulin, cholesterol, triglyceride, HDL cholesterol, PAI-1 activity, PAI-1 antigen and tissue plasminogen activator (tPA) antigen. RESULTS: PAI-1 activity, PAI antigen and tPA antigen were positively correlated with visceral adipose tissue, but not with subcutaneous adipose tissue. This correlation was independent of insulin or triglyceride levels. The amount of visceral adipose tissue explained 28% of the PAI-1 activity variance. Weight loss confirmed this link, PAI-1 diminution being correlated only with visceral adipose tissue loss and not with total fat, insulin or triglyceride decrease. CONCLUSION: This study suggests, like in vitro studies, that visceral fat may be an important contributor to the circulating PAI-1.

Different TH2-TH1 balance in V beta 8 and V beta 6 subsets of splenocytes in NOD females in the early phase of diabetogenesis.

Non-obese diabetic (NOD) mice spontaneously develop T-cell-mediated autoimmune diabetes. Initial work on the diabetogenic T-cell repertoire indicated that autoreactive T lymphocytes were polyclonal but that the presence of specific subsets (V beta 8 or V beta 6) might be required for induction of the disease. Further functional analysis of NOD mice T lymphocytes was limited because of the relative anergic state of these cells due to abnormal patterns of cytokine secretion. The purpose of the present study was to establish experimental conditions allowing the exploration of the functional features of minor T-lymphocyte subsets in vitro using low doses of cofactors. The ability of splenocytes to proliferate, respond to, or secrete interleukin-2 and interleukin-4 was explored in young, pre-diabetic or old non-diabetic female NOD mice. No significant bias in T-cell receptor usage was noted in the spleen of these animals, whereas V beta 6 + lymphocytes could be very efficiently stimulated by interleukin-4 and also produce low but detectable amounts of interleukin-4 during the pre-diabetic period in female NOD mice. These results suggest that diabetes induction is preceded by V beta + subset-specific functional changes in the ability of various T cells to respond to or secrete interleukin-2 and interleukin-4, indicating a functional imbalance of the T-cell repertoire expanded by the autoimmune process.