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Measure of glycosylated hemoglobin.

Glycosylated hemoglobin (HbA1c) is a marker of evaluation of long-term glycemic control in diabetic patients and predicts risks for the development and/or progression of diabetic complications. Glycosylation process depends on the exposure to glucose, so on the half-life of erythrocyte. It was demonstrated, however that metabolic control concerning the last 90-120 days had only a 10% effect on the result of HbAlc; mean blood glucose of the last 30 days contributes for 50% of HbA1c value. Blood glucose value in the afternoon and in the evening better correlate with HbA1c levels if compared with blood glucose values in the morning. It is important to know that there may be, in the evaluation of HbAlc, interference in the dosage, due to a condition of uremia, hyperlipemia, bad conservation and hemolysis of the sample, increase of leucocytes and presence of anomalous hemoglobins. Moreover the use of different methods, the lack of a common calibration concerning the same methods and the variability of instrumentation do not make reproducible results yet, in different laboratories.

Artifacts↗

Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control.

OBJECTIVES: Maintenance of normoglycemia with insulin reduces mortality and morbidity of critically ill patients. Here we report the factors determining insulin requirements and the impact of insulin dose vs. blood glucose control on the observed outcome benefits. DESIGN: A prospective, randomized, controlled trial. SETTING: A 56-bed predominantly surgical intensive care unit in a tertiary teaching hospital. PATIENTS AND INTERVENTION: A total of 1,548 patients were randomly assigned to either strict normalization of blood glucose (80-110 mg/dL) with insulin infusion or the conventional approach, in which insulin is only given to maintain blood glucose levels at 180-200 mg/dL. MEASUREMENTS AND MAIN RESULTS: It was feasible and safe to achieve and maintain blood glucose levels at <110 mg/dL by using a titration algorithm. Stepwise linear regression analysis identified body mass index, history of diabetes, reason for intensive care unit admission, at-admission hyperglycemia, caloric intake, and time in intensive care unit as independent determinants of insulin requirements, together explaining 36% of its variation. With nutritional intake increasing from a mean of 550 to 1600 calories/day during the first 7 days of intensive care, normoglycemia was reached within 24 hrs, with a mean daily insulin dose of 77 IU and maintained with 94 IU on day 7. Insulin requirements were highest and most variable during the first 6 hrs of intensive care (mean, 7 IU/hr; 10% of patients required >20 IU/hr). Between day 7 and 12, insulin requirements decreased by 40% on stable caloric intake. Brief, clinically harmless hypoglycemia occurred in 5.2% of intensive insulin-treated patients on median day 6 (2-14) vs. 0.8% of conventionally treated patients on day 11 (2-10). The outcome benefits of intensive insulin therapy were equally present regardless of whether patients received enteral feeding. Multivariate logistic regression analysis indicated that the lowered blood glucose level rather than the insulin dose was related to reduced mortality (p <.0001), critical illness polyneuropathy (p <.0001), bacteremia (p =.02), and inflammation (p =.0006) but not to prevention of acute renal failure, for which the insulin dose was an independent determinant (p =.03). As compared with normoglycemia, an intermediate blood glucose level (110-150 mg/dL) was associated with worse outcome. CONCLUSION: Normoglycemia was safely reached within 24 hrs and maintained during intensive care by using insulin titration guidelines. Metabolic control, as reflected by normoglycemia, rather than the infused insulin dose, was related to the beneficial effects of intensive insulin therapy.

Blood Glucose↗

Implementation of a safe and effective insulin infusion protocol in a medical intensive care unit.

OBJECTIVE: In a recent randomized controlled trial, lowering blood glucose levels to 80-110 mg/dl improved clinical outcomes in critically ill patients. In that study, the insulin infusion protocol (IIP) used to normalize blood glucose levels provided valuable guidelines for adjusting insulin therapy. In our hands, however, ongoing expert supervision was required to effectively manage the insulin infusions. This work describes our early experience with a safe, effective, nurse-implemented IIP that provides detailed insulin dosing instructions and requires minimal physician input. RESEARCH DESIGN AND METHODS: We collected data from 52 medical intensive care unit (MICU) patients who were placed on the IIP. Blood glucose levels were the primary outcome measurement. Relevant clinical variables and insulin requirements were also recorded. MICU nurses were surveyed regarding their experience with the IIP. RESULTS: To date, our IIP has been employed 69 times in 52 patients admitted to an MICU. Using the IIP, the median time to reach target blood glucose levels (100-139 mg/dl) was 9 h. Once blood glucose levels fell below 140 mg/dl, 52% of 5,808 subsequent hourly blood glucose values fell within our narrow target range; 66% within a "clinically desirable" range of 80-139 mg/dl; and 93% within a "clinically acceptable" range of 80-199 mg/dl. Only 20 (0.3%) blood glucose values were <60 mg/dl, none of which resulted in clinically significant adverse events. In general, the IIP was readily accepted by our MICU nursing staff, most of whom rated the protocol as both clinically effective and easy to use. CONCLUSIONS: Our nurse-implemented IIP is safe and effective in improving glycemic control in critically ill patients.

APACHE↗

The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus.

BACKGROUND: Despite the numerous studies on the relation of albuminuria with increased risk of all-cause mortality in type 2 diabetes mellitus, it remains uncertain whether microalbuminuria and/or gross proteinuria are independent risk factors for cardiovascular mortality. Moreover, the association of albuminuria with cardiovascular mortality in people with type 2 diabetes mellitus has not been well described in US populations. OBJECTIVE: To estimate the relative risks (RRs) for the associations of microalbuminuria and gross proteinuria with cardiovascular disease mortality among persons with older-onset diabetes mellitus. METHODS: We conducted a prospective cohort study of 840 people with older-onset diabetes mellitus who provided urine samples in the 1984-1986 examination of a population-based study of diabetic persons. The presence of microalbuminuria was determined by an agglutination inhibition assay and gross proteinuria by a reagent strip. The main outcome was time to mortality from cardiovascular disease, as determined from death certificates. RESULTS: Of the 840 older-onset diabetic persons, 54.8% had normoalbuminuria, while 24.8% had microalbuminuria and 20.5% had gross proteinuria. During the 12-year follow-up (6127 person-years), we identified 364 deaths from cardiovascular disease. Compared with persons with normoalbuminuria, those with microalbuminuria and gross proteinuria had significantly higher risks of cardiovascular mortality. The RR as controlled for age, sex, glycemic control, insulin use, alcohol intake, physical activity, cardiovascular disease history, antihypertensive use, and retinopathy severity, was 1.84 (95% confidence interval [CI], 1.42-2.40) for those with microalbuminuria and 2.61 (95% CI, 1.99-3.43) for those with gross proteinuria. Further adjustment for other factors did not change the relations we found. When the end point used was mortality from coronary heart disease, stroke, or all causes, the increased risks were significant for both microalbuminuria (adjusted RRs [95% CIs], 1.96 [1.42-2.72], 2.20 [1.29-3.75], and 1.68 [1.35-2.09], respectively) and gross proteinuria (adjusted RRs [95% CIs], 2.73 [1.95-3.81], 2.33 [1.28-4.24], and 2.47 [1.97-3.10], respectively). CONCLUSIONS: Results from our population-based study strongly suggest that both microalbuminuria and gross proteinuria were significantly associated with subsequent mortality from all causes and from cardiovascular, cerebrovascular, and coronary heart diseases. These associations were independent of known cardiovascular risk factors and diabetes-related variables.

Aged↗

A novel advanced glycation index and its association with diabetes and microangiopathy.

Formation of advanced glycation end products (AGEs) is an important mechanism by which chronic exposure to high glucose levels leads to vascular complications. Measurement of AGEs is hence of great importance for clinicians and researchers concerned with the management and prevention of diabetic vascular disease. The aim of this study was to evaluate a simple methodology to detect AGEs in the serum and to correlate their levels with diabetes and microangiopathy, specifically retinopathy and nephropathy. We studied 157 subjects, which included nondiabetic control subjects (n = 38), type 2 diabetic patients without microangiopathy (n = 65), and type 2 diabetic subjects with retinopathy (n = 29) or both retinopathy and nephropathy (n = 25). All subjects were assessed for their glycemic and lipid status. Serum AGEs were monitored by recording the Maillard-specific fluorescence that resulted from sequential addition of serum into the buffer. The resultant linear regression was modeled to yield the slope values that were termed advanced glycation index (AGI) in arbitrary units. The serum levels of AGI (mean +/- SD) were higher in diabetic subjects without complications (6.0 +/- 1.6 units) compared with nondiabetic subjects (4.6 +/- 1.0 units), still higher among diabetic subjects with retinopathy (7.6 +/- 1.2 units) and highest in diabetic subjects with both retinopathy and nephropathy (8.3 +/- 2.0 units). Among diabetic subjects, AGI had a significant positive correlation with duration of diabetes (r = 0.25, P = .006), glycated hemoglobin (r = 0.27, P = .004), cholesterol (r = 0.24, P = .009), triglycerides (r = 0.23, P = .014), and serum creatinine (r = 0.30, P = .001), and a significant negative correlation with creatinine clearance (r = -0.27, P = .003). Logistic regression analysis using diabetic microangiopathy as the dependent variable showed an association with AGI even after including age, duration of diabetes, and glycated hemoglobin (P < .001) into the model. Advanced glycation index is a simple method to detect AGEs, and it correlates well with diabetes, particularly with microangiopathy.

Aged↗

Comparison between continuous subcutaneous insulin infusion and multiple insulin injection therapy in type 1 diabetes mellitus: 18-month follow-up.

OBJECTIVE: To compare the results with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) of insulin in the treatment of type 1 diabetes during 18 months of follow-up. METHODS: We prospectively studied 29 patients with type 1 diabetes in Brazil; 17 patients elected to change from conventional insulin therapy (2 injections daily) (N = 3) or MDI (N = 14) to CSII therapy, and the other 12 continued to receive MDI therapy. All patients were treated with insulin lispro; patients in the MDI treatment group also received NPH insulin. We compared hemoglobin A1c (HbA1c) values, determined at baseline and every 3 months, between the two treatment groups. Other variables analyzed included weight, body mass index, total daily dose of insulin, and incidence of severe hypoglycemia. RESULTS: Patients in the CSII group had a significant decrease (P<0.001) in mean HbA1c at 18 months in comparison with baseline (8.3% versus 6.5%). In the MDI group, no significant changes were found in mean HbA1c. After 3 months of treatment, patients in the CSII group had a significantly lower mean HbA1c level than did patients receiving MDI (P<0.05). Of the 17 patients treated with CSII, all had HbA1c values less than 7.5% at 18 months, and 13 (76%) had HbA1c levels less than 7%. Although no significant variations in weight were observed in either group, the insulin/weight ratio decreased in the CSII group from baseline to 18 months (0.8 U/kg to 0.6 U/kg; P = 0.02). No episodes of severe hypoglycemia were noted in either group. CONCLUSION: Patients with diabetes treated with insulin lispro have better glycemic control with CSII than with MDI. Most of our patients in the CSII group were able to achieve target HbA1c levels less than 7% at 18 months without an increase in hypoglycemic episodes.

Adolescent↗

Glycemic effects of intensive caloric restriction and isocaloric refeeding in noninsulin-dependent diabetes mellitus.

To assess the effects of very low caloric (VLC) diets on glucose homeostasis in noninsulin-dependent diabetes mellitus, 30 obese subjects with NIDDM were studied for 40 days while eating a 330 Cal/day diet, with a subgroup of 12 subjects further evaluated during 40 days of refeeding. All subjects successfully lost weight, with an average weight loss of 4.6 +/- 0.2 kg (+/- SEM) after 10 days, 7.1 +/- 0.3 kg after 20 days, and 10.5 +/- 0.4 kg after 40 days of VLC diet therapy. Thus, weight loss was steady and progressive throughout the diet period. In contrast, the majority (87%) of the reduction in mean fasting plasma glucose (FPG) levels (297 +/- 13 to 158 +/- 10 mg/dl; P less than 0.001) occurred after 10 days of VLC diet therapy, with a further reduction in glucose levels to 138 +/- 9 mg/dl on day 40. The FPG response measured after 10 days of VLC diet was unrelated to the degree of obesity, rate or extent of weight loss, or prevailing insulin levels, but did correlate significantly with the initial FPG level (r = 0.37; P less than 0.05) and duration of diabetes (r = 0.42; P less than 0.05). After discontinuation of the VLC diet and refeeding of an isocaloric (weight maintenance) diet in 12 subjects, a variable increase in the FPG occurred, with an average increase of 80% after 40 days of refeeding. However, the mean FPG level after 40 days of refeeding was still markedly lower than that before VLC diet therapy (254 +/- 20 vs. 167 +/- 14 mg/dl; P less than 0.02) despite withdrawal of antidiabetic medication in all subjects. The basal hepatic glucose output (HGO) fell rapidly from 149 +/- 13 to 81 +/- 5 mg/M2 X min (P less than 0.001) after 10 days of VLC diet and rose from 67 +/- 4 to 88 +/- 7 mg/M2 X min (P less than 0.001) after 10 days of refeeding. Basal HGO demonstrated a highly significant positive correlation with FPG levels (r = 0.89; P less than 0.001) before and during both VLC diet therapy and refeeding. A significant correlation was also found between the change in FPG level and the change in basal HGO (r = 0.84; P less than 0.001) during both VLC diet and refeeding. Compared to that before the VLC diet, glucose tolerance to mixed meals was markedly improved during the refeeding period, with no change in circulating insulin levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Birth trauma in insulin-dependent diabetic pregnancies.

Infants of insulin-dependent diabetic mothers are considered to be at high risk for birth trauma, presumably due to macrosomia. With current management of diabetes in pregnancy, including strict glycemic control, the rate and the severity of macrosomia should be decreased. The frequent use of ultrasound to assess fetal growth and weight and the use of cesarean delivery in case of fetal macrosomia should further decrease the risk for birth trauma in these infants. We therefore undertook this study to test the null hypothesis that with current management, insulin-dependent diabetic mothers have a rate of birth trauma similar to that of infants of nondiabetic mothers (normal glucose challenge test at 28 weeks' gestation) matched for gestational age at birth, presence or absence of labor, delivery method (vaginal versus cesarean), and race. We studied 118 insulin-dependent diabetic mothers (White classes B-RT) and 354 control subjects (three matches for each insulin-dependent diabetic mother). The rate of birth trauma was 3.4% in insulin-dependent diabetic mothers, not significantly different from controls (2.5%). Logistic regression analysis in which birth trauma was the dependent variable and diabetes, race, presence or absence of labor, mode of delivery (vaginal versus cesarean), infant weight, and infant head circumference were independent variables revealed that only vaginal delivery was a significant risk factor for birth trauma in infants in both groups (p = 0.01). Most frequently observed birth traumas were brachial plexus injury, facial nerve injury, and cephalohematoma. Of the three infants with brachial plexus injury (insulin-dependent diabetic mothers, two; controls, one), two were delivered with use of midforceps.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The postpartum metabolic outcome of women with previous gestational diabetes mellitus.

BACKGROUND: This study investigated postpartum metabolic abnormality in women with previous gestational diabetes mellitus (GDM) and predictive factors for postpartum glucose intolerance. METHODS: From March 2001 to February 2003, 127 prior-GDM women underwent a 75g oral glucose tolerance test (OGTT) and metabolic assessment at least six weeks after delivery. To identify the predictors, clinical variables obtained at the time of GDM were compared. RESULTS: The cumulative incidence rates of diabetes mellitus (DM) and abnormal glucose tolerance (AGT) i.e. impaired fasting glucose or impaired glucose tolerance, in women with previous GDM were 13.4% and 29.1%, respectively. Postpartum body mass index (BMI), total cholesterol, HDL cholesterol, triglycerides, blood pressure, waist-to-hip ratio and fasting C-peptide were not significantly different among DM, AGT and normal glucose tolerance (NGT) women. However, the C-peptide/glucose score was lower in DM than in AGT and NGT women (p < 0.01). DM or AGT women had higher prepregnancy BMI and fasting glucose level for 100g OGTT than NGT women (p < 0.05) at the time of GDM. The fasting glucose value was an independent risk factor. The cutoff point of three abnormal values in 100g OGTT provided 86% sensitivity and 43% specificity for the prediction of postpartum DM or AGT. CONCLUSIONS: High prepregnancy BMI and increased glycemic deterioration at the time of GDM are found in women developing postpartum DM and AGT. The fasting glucose value for 100g OGTT is an independent risk factor and more than three abnormal glucose values offers good diagnostic efficacy in predicting postpartum glucose intolerance.

Adult↗

Determination of the glycaemic index of foods: interlaboratory study.

OBJECTIVE: Practical use of the glycaemic index (GI), as recommended by the FAO/WHO, requires an evaluation of the recommended method. Our purpose was to determine the magnitude and sources of variation of the GI values obtained by experienced investigators in different international centres. DESIGN: GI values of four centrally provided foods (instant potato, rice, spaghetti and barley) and locally obtained white bread were determined in 8-12 subjects in each of seven centres using the method recommended by FAO/WHO. Data analysis was performed centrally. SETTING: University departments of nutrition. SUBJECTS: Healthy subjects (28 male, 40 female) were studied. RESULTS: The GI values of the five foods did not vary significantly in different centres nor was there a significant centrexfood interaction. Within-subject variation from two centres using venous blood was twice that from five centres using capillary blood. The s.d. of centre mean GI values was reduced from 10.6 (range 6.8-12.8) to 9.0 (range 4.8-12.6) by excluding venous blood data. GI values were not significantly related to differences in method of glucose measurement or subject characteristics (age, sex, BMI, ethnicity or absolute glycaemic response). GI values for locally obtained bread were no more variable than those for centrally provided foods. CONCLUSIONS: The GI values of foods are more precisely determined using capillary than venous blood sampling, with mean between-laboratory s.d. of approximately 9.0. Finding ways to reduce within-subject variation of glycaemic responses may be the most effective strategy to improve the precision of measurement of GI values.

Adult↗

[Glycemia and the levels of free fatty acids in small-for-date born infants after monosaccharide load. Communication I (author's transl)].

In order to evaluate some aspects of carbohydrate metabolism in small-for-date born infants the authors have performed in them the glucose tolerance test. The glycemic reflex was estimated in relation to the free fatty acids level (FFA). This was done twice a year in the first half year of life and in the second one. We compared the results with data obtained form full-size born infants tested in the same of time. The group of small-for-date born (SRDB) infants included 23 infants in the first half year and 12 in the second one. The SFDB infants were loaded with glucose and galactose given to them in a dosis of 1 g of each sugar in a 15% solution. The following micromethods were applied: Hyvarinen and Nikkila for glucose, and Dole and Meinertz in Novak's modification for FFA. The level of glucose and FFA were estimated at fasting and after loading at 20, 40, 90, 120 and 180 minutes. In order to be able to evaluate the results, the authors performed the variance analysis. On the basis a significantly higher variability of FFA levels was found in comparison with glucose levels as well as a variability of the two parameters significantly higher in small-for-date born infants than in full-size born infants. In spite of that in standarized mean values a relationship between glucose and FFA levels was found in small-for-date born infants opposite to that in full-size born infants. In the former the glucose levels and free fatty acids were higher then in the latter. This phenomenon disappeared in the second half-year of life. The disappearance rate (as measured by coefficient K) was slightly higher than in the second half year. In the second half year this difference was not noted between the observed parameters in two groups of infants. If it may be concluded on the basis of the authors' observations, the higher levels of glucose in small-for-date born infants in their first half year of life could indicate some disturbance in glucose utilization and the higher level of FFA then usually found in fullsize born infants during the oral glucose tolerance test might be an additional proof for the above.

Age Factors↗

Increased 24 h mean insulin-like growth factor binding protein-3 proteolytic activity in pubertal type 1 diabetic boys.

Hyperglycaemia and increased variability of blood glucose in pubertal children with type 1 diabetes may be related to increased growth hormone (GH) secretion and insulin resistance. The role of changes in insulin-like growth factor-I (IGF-I) bioavailability for the glycaemic control in these patients has not been completely elucidated. In particular, the possible role of increased IGF binding protein-3 (IGFBP-3) proteolysis reported in other insulin resistant states awaits further characterization. The aims of this study were to assess if hyperglycaemia in children with type 1 diabetes was associated with changes in free dissociable IGF-I (fdIGF-I) and IGF binding protein-3 protease activity (IGFBP-3-PA) and if increased insulin resistance during puberty was associated with changes in IGFBP-3-PA in healthy and diabetic children. In diabetic boys in the period of maximal linear growth (Tanner stage 3, n = 5), the mean level and the variability of IGFBP-3-PA, determined every second hour throughout 24 h, were significantly higher both compared to postpubertal diabetic boys (n = 6; P = 0.003 and P = 0.001, respectively), and to age matched healthy boys (n = 4; P = 0.006 and P < 0.001 respectively). This activation of IGFBP-3-PA was most prominent during the day time. The mean 24 h blood glucose level (determined hourly) was the only parameter studied that significantly predicted the changes in mean 24 h IGFBP-3-PA in the diabetes group. The mean 24 h concentrations of fdIGF-I were decreased in the diabetic boys compared to the healthy controls but statistical significance was only achieved in Tanner Stage 5 (p = 0.03). We speculate that the elevated levels of IGFBP-3-PA in Tanner 3 diabetic boys are related to deteriorated glucose homeostasis and that it may be a compensatory mechanism to attenuate the decrease in fdIGF-I in order to partly restore insulin sensitivity and glycemic control.

Adolescent↗

Exercise training improves baroreflex sensitivity in type 2 diabetes.

Type 2 diabetes is a strong risk factor for coronary heart disease and sudden cardiac death. It is associated with reduced baroreflex sensitivity (BRS) and heart rate variability (HRV), which are indicators of increased risk for mortality and morbidity in various patient populations. This study was designed to assess the effects of exercise training on BRS, HRV, and hemodynamics in patients with type 2 diabetes. Subjects (50 men, mean age 53.3 +/- 5.1 years) with type 2 diabetes were randomized into either a control group, in which they received conventional treatment only, or an exercise group, in which they received conventional treatment together with heart rate-controlled endurance training twice a week and supervised muscle strength training twice a week for 12 months. Measurements taken at baseline and follow-up included VO(2max), standard time and frequency domain measures of HRV during 24-h recording, and BRS by the phenylephrine method. Cardiac index, systemic vascular resistance index, stroke index, and pulse wave velocity were measured by whole-body impedance cardiography. Significant improvements in VO(2max) (exercise group: +2.3 ml x kg(-1) x min(-1); P < 0.005 vs. control group), muscle strength, and glycemic control (exercise group: HbA(1c) -0.9%; P < 0.001 vs. control group) were observed in the exercise group. BRS increased in the exercise group, from 6.8 to 8.6 ms/mmHg, and decreased in the control group, from 7.5 to 6.4 ms/mmHg (95% CI for the difference between 0.05 and 4.36 ms/mmHg; P < 0.05). No significant changes in the time or frequency domain measures of HRV or in systemic hemodynamics were observed. We concluded that exercise training improves BRS sensitivity in type 2 diabetes subjects in addition to increasing the exercise capacity and muscle strength and improving glucose control. These beneficial effects in reflectory autonomic regulation and glucose control caused by exercise may be associated with improved prognosis of type 2 diabetes patients.

Baroreflex↗

A randomized controlled trial of weight reduction and exercise for diabetes management in older African-American subjects.

OBJECTIVE: To evaluate a weight loss and exercise program designed to improve diabetes management in older African-Americans. RESEARCH DESIGN AND METHODS: Overweight African-Americans (n = 64) ages 55-79 years with NIDDM were randomized to either an intervention (12 weekly group sessions, 1 individual session, and 6 biweekly group sessions) or usual care (1 individual session, and 6 biweekly group sessions) or usual care (1 class and 2 informational mailings). Clinical and behavioral variables were assessed at 0, 3, and 6 months of treatment. RESULTS: Significant net differences in the intervention versus usual care were observed for weight (-2.0 kg, P = 0.006), physical activity, and dietary intake of fat, saturated fat, cholesterol, and nutrition knowledge at 3 months (all P < 0.05) and for weight at 6 months (-2.4 kg; P = 0.006) and mean HbA1c values at 3 and 6 months (respectively, -1.6 and -2.4%, both P < 0.01). After the adjustment for changes in weight and activity, the intervention participants were approximately twice as likely to have a one unit decrease in HbA1c value as those in usual care. Blood pressure increase sin usual care participants resulted in net differences (intervention minus control) at 3 and 6 months of -3.3 (P = 0.09) and -4.0 (P = 0.05) mmHg diastolic, respectively, and -8.4 (P = 0.06) and -5.9 (P > 0.10) mmHg systolic, respectively. Blood lipid profiles improved more in intervention than usual care participants, but not significantly. CONCLUSIONS: The intervention program was effective in improving glycemic and blood pressure control. The decrease in HbA1c values was generally independent of the relatively modest changes in dietary intake, weight, and activity and may reflect indirect program effects on other aspects of self-care.

Black or African American↗

Poor glycemic control predicts coronary heart disease events in patients with type 1 diabetes without nephropathy.

Patients with type 1 diabetes mellitus, especially those with nephropathy, are at increased risk for coronary heart disease (CHD). However, information on the predictive value of cardiovascular risk factors and the degree of hyperglycemia with respect to CHD events in patients with type 1 diabetes without nephropathy is still incomplete. Therefore, we performed a prospective study on risk factors for CHD in patients with type 1 diabetes free of clinical nephropathy. At baseline examination, cardiovascular risk factor levels of CHD were determined in 177 patients with type 1 diabetes (87 men and 90 women), age 45 to 64 years at baseline and >/=30 years at the time of diagnosis of diabetes. These patients were followed up to 7 years with respect to CHD events. Altogether, 20 patients with type 1 diabetes (13 men [7.3%] and 7 women [3.9%]) died of CHD and 28 patients with type 1 diabetes (17 men [9.6%] and 11 women [6.2%]) had a serious CHD event (death from CHD or nonfatal myocardial infarction). In multivariate Cox regression analysis, a previous history of myocardial infarction (hazard ratio [HR] and its 95% confidence interval, 8.0 [3.1 to 21.0], P<0.001), high glycohemoglobin A1 (>10.4%, the highest tertile, HR 5.4 [1.4 to 20.4], P=0.013), and the duration of diabetes (>16 years, the highest tertile, HR 4.2 [1.3 to 12.9], P=0.013) were the only variables associated with CHD death even after adjustment for other cardiovascular risk factors. These variables also predicted the incidence of all CHD events. Our results indicate that poor metabolic control is a strong predictor of CHD events in patients with late-onset type 1 diabetes without nephropathy, independently of other cardiovascular risk factors.

Aged↗

Use of fetal ultrasound to select metabolic therapy for pregnancies complicated by mild gestational diabetes.

OBJECTIVE: To determine whether fetal ultrasound early in the third trimester can identify Latina with mild gestational diabetes mellitus (GDM) whose fetuses are at risk for macrosomia and, if so, whether maternal insulin therapy can reduce that risk. RESEARCH DESIGN AND METHODS: Study subjects included 303 consecutive women with GDM and a fasting serum glucose level < 5.8 mM on diet therapy who had a fetal ultrasound between 29 and 33 weeks gestation. Of the women, 98 (32%) had a fetal AC > or = 75th percentile for gestational age, and 59 women completed a randomized trial of diet therapy (n = 29) or diet plus twice daily insulin (n = 30). Maternal nutrient levels were assessed by meal tolerance testing (MTT) before and during therapy and by capillary glucose monitoring four to seven times a day. Birth weights corrected for gestational age and neonatal glycemia and skin folds were the primary outcome variables compared between treatment groups. RESULTS: Diet and diet-plus-insulin groups were well matched for maternal age, prepregnancy relative weight, weight gain during pregnancy, and glycemia at entry. Insulin therapy reduced maternal capillary (P < 0.005) and MTT (P < 0.001) glucose levels and prevented a diet-associated rise in MTT triglyceride levels (P < 0.002). Gestational age at delivery was similar in insulin- and diet-treated groups (39.6 +/- 0.2 vs. 39.5 +/- 0.2 weeks). Birth weights (3,647 +/- 67 vs. 3,878 +/- 84 g; P < 0.02), the prevalence of large-for-gestational age infants (13 vs. 45%, P < 0.02), and neonatal skin-fold measurements at three sites (P < 0.005) were reduced in the insulin-treated group. Rates of transient neonatal hypoglycemia were low in both treatment groups (14 and 18%, respectively) and did not differ significantly between groups. CONCLUSIONS: Fetal ultrasound early in the third trimester identified women with mild GDM whose infants were at high risk for fetal macrosomia in the absence of standard glycemic criteria for insulin therapy. Insulin treatment reduced the macrosomia, indicating that fetal ultrasound can be used to guide metabolic therapy in pregnancies complicated by mild GDM.

Analysis of Variance↗

Glomerular hyperfiltration in non-proteinuric and non-hypertensive Japanese type 2 diabetic patients.

Glomerular hyperfiltration (GHF) may be an important factor in the initiation of glomerular damage and in predisposing diabetic patients to the later development of diabetic nephropathy (DN). Previous reports show wide range of prevalence of GHF in type 2 diabetic patients. This cross-sectional study was designed to determine the prevalence of GHF at an early stage of DN in Japanese type 2 diabetic patients and to investigate the relationships between clinical variables and GHF. We measured the glomerular filtration rate (GFR) using the plasma clearance of iohexol in 56 control subjects and 93 type 2 diabetic patients without hypertension or overt proteinuria. We used Altman's method to calculate the age-adjusted 95% reference ranges for GFR from the data of control subjects and classified GHF in type 2 diabetics from the reference ranges. Hyperfiltrators (defined as GFR > mean GFR + 1.96 S.D. of control subjects) was found in 17% patients (16/93). Other 77 patients (83%) were normofiltrators (defined as GFR< or = mean GFR + 1.96 S.D. of control subjects). GFR values, both in hyperfiltrators and normofiltrators, were 140.5 +/- 14.6 and 98.8 +/- 14.0 ml/min/1.73 m2, respectively. Age, sex, BMI, blood pressure, albumin excretion rate, and frequency of microalbuminuria did not differ between the hyperfiltrators and normofiltrators. Fasting plasma glucose and hemoglobin A1c were significantly higher in the hyperfiltrators than the normofiltrators (P<0.001 and 0.004, respectively). GHF exists among Japanese type 2 diabetic patients with no evidence of overt proteinuria or hypertension. Glycemic control might be a significant determinant of GHF in these patients.

Adult↗

Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of nonalcoholic fatty liver disease.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can lead to hepatic fibrosis and cirrhosis. Portal fibrosis in the absence of NASH, called isolated portal fibrosis (IPF), has received less attention and has not been classified as a spectrum of NAFLD. The aims of this study were to determine the prevalence of IPF in subjects undergoing gastric bypass surgery, to identify biochemical variables associated with IPF, and to assess the metabolic syndrome as defined by the AdultTreatment Panel III criteria. We analyzed liver biopsies from 195 morbidly obese subjects after excluding all other causes of liver disease. The prevalence of fatty liver (FL) only, IPF, and NASH was 30.3%, 33.3%, and 36.4%, respectively. Several biochemical parameters significantly trended across the 3 groups, with IPF falling between FL and NASH. Hyperglycemia was the only metabolic parameter associated with NASH (OR, 5.4; 95% CI, 2.4-12; P < .0001) and IPF (OR, 2.8; 95% CI, 1.2-6.5; P = .01). Subjects with diabetes had the greatest risk for NASH (OR, 8; 95% CI, 3.3-19.7; P < .0001) and IPF (OR, 4.3; 95% CI, 1.6-11.6; P = .003). The metabolic syndrome was identified in 78.5% of subjects, and a significant trend for the number of metabolic criteria was observed across the spectrum of FL, IPF, and NASH. In conclusion, a significant subset of morbidly obese individuals has portal fibrosis in the absence of NASH that is associated with glycemic dysregulation. Therefore, IPF should be considered a spectrum of NAFLD that may prelude NASH in morbid obesity.

Adult↗