OBJECTIVE -This study was designed to assess the insulin-sparing effect of oral administration of metformin along with a continuous subcutaneous insulin infusion (CSII) for the treatment of type 1 diabetic patients.RESEARCH DESIGN AND METHODS -A total of 62 patients (25 women and 37 men) were studied in a monocenter, randomized, double-blind placebo-controlled study, comparing metformin (850 mg b.i.d.) with placebo in association with CSII during a 6-month period.RESULTS -Treatment with metformin was associated with a reduction in daily insulin requirements between V0 and V6 of Ϫ4.3 Ϯ 9.9 units (Ϫ7.8 Ϯ 18%) compared with an increase with placebo treatment of 1.7 Ϯ 8.3 units (2.8 Ϯ 12.7%) (P ϭ 0.0043). A decrease in basal requirement of insulin was also observed in patients treated with metformin of Ϫ2.6 Ϯ 3.2 units (Ϫ7.9 Ϯ 23.8%) compared with an increase with placebo treatment of 1.9 Ϯ 5.7 units (8.8 Ϯ 27.1%) (P ϭ 0.023). HbA 1c remained unchanged in treatment with metformin and placebo between V0 and V6. The number of hypoglycemic events (Ͻ60 mg/dl) was similar in both groups. Significant reductions of total cholesterol (P ϭ 0.04) and LDL cholesterol (P ϭ 0.05) were observed in patients treated with metformin. Gastrointestinal events, including diarrhea and abdominal pain, were reported in three patients in the metformin group who discontinued the trial. Mild or moderate gastrointestinal side effects were also reported in eight patients treated with metformin and two patients treated with placebo (P ϭ 0.069).CONCLUSIONS -Metformin was found to be a safe insulin-sparing agent, when used in combination with CSII for the treatment of type 1 diabetes.

OBJECTIVE -This study was designed to test the accuracy of capillary ketonemia for diagnosis of ketosis after interruption of insulin infusion. RESEARCH DESIGN AND METHODS-A total of 18 patients with type 1 diabetes treated by external pump were studied during pump stop for 5 h. Plasma and capillary ketonemia and ketonuria were determined every hour from 7:00 A.M. (time 0 min ϭ T0) to 12:00 P.M. (time 300 min ϭ T300). Plasma ␤-hydroxybutyrate (␤-OHB) levels were measured by an enzymatic end point spectrophotometric method, and capillary ␤-OHB levels were measured by an electrochemical method (MediSense Optium meter). Ketonuria was measured by a semiquantitative test (Ketodiastix). Positive ketosis was defined by a value of Ն0.5 mmol/l for ketonemia and Ն4 mmol/l (moderate) for ketonuria. RESULTS-After stopping the pump, concentrations of ␤-OHB in both plasma and capillary blood increased significantly at time 60 min (T60) compared with T0 (P Ͻ 0.001), reaching maximum levels at T300 (1.30 Ϯ 0.49 and 1.23 Ϯ 0.78 mmol/l, respectively). Plasma and capillary ␤-OHB values were highly correlated (r ϭ 0.94, P Ͻ 0.0001). For diagnosis of ketosis, capillary ketonemia has a higher sensitivity and negative predictive value (80.4 and 82.5%, respectively) than ketonuria (63 and 71.8%, respectively). For plasma glucose levels Ն250 mg/dl, plasma and capillary ketonemia were found to be more frequently positive (85 and 78%, respectively) than ketonuria (59%) (P ϭ 0.017). The time delay to diagnosis of ketosis was significantly higher for ketonuria than for plasma ketonemia (212 Ϯ 67 vs. 140 Ϯ 54 min, P ϭ 0.0023), whereas no difference was noted between plasma and capillary ketonemia.CONCLUSIONS -The frequency of screening for ketosis and the efficiency of detection of ketosis definitely may be improved by the use of capillary blood ketone determination in clinical practice. Diabetes Care 26:1137-1141, 2003T he Diabetes Control and Complications Trial (DCCT) has demonstrated that intensive diabetes management, multiple daily injections (MDI) in two-thirds of cases, and continuous subcutaneous insulin infusion (CSII) in one-third of cases could reduce the risk of development and progression of long-term complications of type 1 diabetes (1). CSII provides the most physiological pattern of insulin delivery currently available (2). However, it is now clearly established that CSII is associated with a substantial increase in risk of diabetic ketoacidosis (DKA) compared with MDI (3,4). In a meta-analysis of 14 studies, odds ratios (95% CI) were 7.20 (2.95-17.58) for exclusive use of insulin pumps compared with 1.13 (0.15-8.35) for MDI (4). Technical problems with CSII (pump failure, catheter occlusion, skin infection) may reduce insulin delivery or insulin absorption and cause DKA (5). Currently, the use of short-acting insulin analogs in external pumps is becoming more widespread because some studies have shown that the use of such analogs provides better glycemic control and stability than regular insulin (6 -8). Considering the pha...

OBJECTIVE -Performance criteria have been established for in vitro blood glucose monitoring, particularly for the self-monitoring of blood glucose using glucose meters. Devices intended for use in the future, such as the continuous glucose monitoring system (CGMS), should satisfy similar criteria, particularly in diabetic patients under intensive therapy.RESEARCH DESIGN AND METHODS -The analysis was conducted on 18 type 1 diabetic patients (not controlled, HbA 1c Ͼ7.5%) treated by external pump using insulin analogs. Each patient received a glucose sensor for 3 days during his/her hospitalization and was instructed in its operation. Medtronic criteria were used to determine the accuracy of the CGMS. In addition, the data were analyzed according to American Diabetes Association (ADA) criteria, Clarke Error Grid analysis, and method of residuals, with the glucose oxidase method using a Beckman analyzer used as the reference method. Specificity and sensitivity were evaluated from the viewpoint of accuracy in the detection of hypoglycemia. For nine patients, two glucose sensors were simultaneously inserted into an abdominal site to determine the reproducibility of the system. RESULTS -Among the 33 glucose sensors inserted, 6 (18%) were nonfunctional. The mean duration of CGMS recording was 63 Ϯ 12 h. From all of the 692 sets of data that paired glucose readings and CGMS, the coefficients of correlation ranged from 0.87 to 0.92 and the mean absolute error ranged from 12.8 to 15.7%. The time experienced in hypoglycemia (Ͻ55 mg/dl) was reported at 86 Ϯ 62 min/day. Only 39% of the CGMS values satisfied the ADA precision criteria to within Ϯ10%, and 19% of these values satisfied the future ADA precision criteria of accuracy to within Ϯ5%. The means of difference method showed that the CGMS slightly underestimated the plasma glucose values (mean ϭ Ϫ12 mg/dl). Error grid analysis showed only 77% of the glucose sensor values were in zone A, and 98.9% were in zones A and B. Two values fell in zone C and a single value fell in zone D. The sensitivity and specificity of the CGMS to detect hypoglycemia were 33 and 96%, respectively. A total of 6,666 paired sensor values were recorded with a coefficient of correlation of 0.84 with a coefficient of variation of 8.25%.CONCLUSIONS -CGMS could be useful in routine clinical practice to provide much more information on the glucose profile than intermittent self-monitoring of blood glucose (SMBG). However, CGMS cannot be used as a replacement for glucose meters because it does not satisfy the conventional performance goals set down for in vitro glucose measurements and could therefore lead to clinically incorrect treatment decisions. Diabetes Care 26:582-589, 2003

No abstract

OBJECTIVES:The present study was undertaken to assess the differential impact of insulin resistance, leptin and body composition on myocardial mass and serum markers of cardiac fibrosis in obese subjects, within a small range of elevated BMI (30-40 kg/m 2 ), without pulmonary disease, cardiovascular disease, hypertension, cardiac hypertrophy or other cardiovascular disease. BACKGROUND: Obesity is an independent predictor of left ventricular mass (LVM) and is associated with disturbances in cardiac structure. The extent of the interstitial fibrosis in obese patients is not known, especially in the absence of cardiac hypertrophy. METHODS AND RESULTS:We included 160 obese subjects. The LVM was obtained using the Devereux formula. Body composition was estimated from a total body scan. Insulin sensitivity was assessed by homeostasis model assessment (HOMA), and cardiac collagen turnover by measurement of procollagen type III aminopeptide (PIIINP). PIIINP was correlated to the E/A ratio (r ¼ 0.24; P ¼ 0.012), a marker of ventricular function. PIIINP was independently correlated with glucose concentration (r ¼ 0.27; P ¼ 0.004), indexes of insulin resistance (HOMA (r ¼ 0.27; P ¼ 0.003), insulin (r ¼ 0.24; P ¼ 0.008)), and parameters associated with the insulin-resistance syndrome (HDL-cholesterol r ¼ À0.27; P ¼ 0.004) and fat trunk/fat leg ratio (r ¼ 0.24; P ¼ 0.053)). The variable most correlated with PIIINP was HDL-cholesterol, followed by HOMA (r 2 ¼ 0.13). When HOMA was substituted for blood glucose concentration and insulinemia (Model 2), HDL-cholesterol was strongly related to lower PIIINP levels, followed by higher glucose concentration (r 2 ¼ 0.21). Regression analyses showed that LVM had the strongest independent positive correlation with fat-free mass (FFM) (r ¼ 0.39; P ¼ 0.0002), followed by systolic blood pressure (r ¼ 0.19; P ¼ 0.034). Neither adipose mass nor height independently added information to multivariate models. The ratio leptin/fat mass was correlated with LVM (r ¼ À0.27; P ¼ 0.004), but not independently of the FFM. Markers for fibrosis were not significantly correlated with LVM. As a result, FFM was the most predictive factor of LVM in obese subjects. CONCLUSION: We found that serum levels of markers of cardiac collagen synthesis were significantly associated with insulin resistance in normotensive, nondiabetic obese subjects, and not related to the LVM. As a result, PIIINP could be a very early marker of ventricular dysfunction in these patients. Furthermore, we suggest that, for better detection of left ventricle hypertrophy in obese subjects, LVM should be indexed to FFM rather than to body surface area, or height.

Concentric remodeling is frequently documented by MRI in the middle-aged men with abdominal obesity and in association with a decrease in TAC no longer counter-balanced by a decrease in TPVR, suggesting a remodeling from proximal to peripheral vasculature.

No abstract

Objective: Patients with chronic pancreatitis suffer from malabsorption and nutritional deficiencies. However there is little data available concerning the fatty acid profile in chronic pancreatitis. Diabetes mellitus, a common complication of this disease, could interfere with the metabolism of fatty acids. Subjects: We therefore compared the fatty acid composition of LDL from four groups of male patients with (a) chronic pancreatitis without diabetes (ND-CP; n ¼ 12), (b) diabetes secondary to chronic pancreatitis and insulin-treated (CP-D; n ¼ 35); (c) type 1 diabetes (n ¼ 25); and (d) controls (n ¼ 20). Results: The patients in both groups of chronic pancreatitis (ND-CP and CP-D) had lower mean values for linoleic acid than that seen in the type 1 DM and control groups, whereas monounsaturated fatty acids (MUFA; 18 : 1(n-9) and (16 : 1(n-7)) were significantly increased in these two groups (ND-CP and CP-D). Docosa-hexaenoic-acid (22 : 6(n-3)) was significantly decreased in the CP-D group (P > 0.05), a response that could be explained by the effects of diabetes mellitus and by selenium deficiency. In this way, diabetes was associated with a decrease in the docosa-hexaenoic-acid (22 : 6(n-3); r ¼ 0.30, P ¼ 0.005), and selenium was correlated with DHA (r ¼ 0.28, P ¼ 0.029) and with the 22 : 6(n-3)=20 : 5(n-3) ratio (evaluating the delta 4 desaturation); r ¼ 0.31, P ¼ 0.022), independently of the diabetes effect. Selenium was negatively correlated with 20 : 4(n-6)/ 20 : 3(n-6) ratio (evaluating the delta 5 desaturase; r ¼ -0.30; P ¼ 0.025). These results suggest that these two factors may have a role in the regulation of the desaturation process. If we consider that a ratio of 16 : 1(n-7)=18 : 2(n-6) greater than 0.086 in plasma indicates an EFAn-6 deficiency, 40% of our CP patients, 57.6% of CP-D patients and 13.6% of type 1 DM patients were involved. Conclusions: The consequences of these deficiencies are not evaluated in this disease. However, correction of the fundamental deficiencies in essential fatty acids and in selenium seems desirable in chronic pancreatitis.