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Biomedical subjects

D J Becker

Publications and source records attributed to D J Becker.

At least 37 records · Page 2Linked to original sources
PubMed1999

Leptin before and after insulin therapy in children with new-onset type 1 diabetes.

Serum leptin levels reflect the amount of body fat. However, several reports suggest that insulin may also regulate serum leptin levels. This study was aimed at testing whether leptin levels are low in newly diagnosed patients with type 1 diabetes and increase after institution of insulin therapy. Nineteen children with new-onset type 1 diabetes were studied. Serum leptin levels were measured at presentation before insulin therapy was initiated (day 0), 1 day after insulin therapy (day 1), 3-5 days after insulin therapy (day 3-5), and at 3 months of follow-up (3 months). The control group consisted of 19 healthy children matched for age and body mass index. On day 0 leptin levels were lower in the patients compared with those in controls (3.3 +/- 0.2 vs. 6.2 +/- 0.9 ng/mL; P < 0.005). After insulin therapy, leptin levels increased significantly by day 1 without significant weight change and became comparable to control values by days 3-5. Before insulin therapy, leptin did not correlate with weight, body mass index, or hemoglobin A1c. After insulin therapy, leptin levels on days 3-5 correlated with insulin dose (r = 0.43; P = 0.03). The results of this study demonstrate that children with new-onset type 1 diabetes have low leptin levels before insulin therapy. Leptin levels increase within 24 h of insulin therapy and become comparable to nondiabetic levels by 3-5 days. This rapid increase in leptin after 24 h of insulinization is independent of changes in body weight and is postulated to be due to a stimulatory effect of insulin on leptin production, nutritional replenishment, or both factors together.

Adipose Tissue↗
PubMed1999

Transfection of adipocytes by gene gun-mediated transfer.

Studies of the gene expression, metabolism and intracellular signaling of adipocytes have been hindered by the difficulty of transfecting cultured adipocytes using standard methods. Here, we demonstrate the utility of gene gun-mediated genetic transfer for transfection of differentiated 3T3-L1 adipocytes. Transfection of adipocytes with the Helios Gene Gun yielded a transfection efficiency that was consistently 5%-10% of total cells. We have used this technique to overexpress the transcription factor CCAAT/Enhancer Binding Protein alpha (C/EBP alpha) and transactivate an obese gene promoter-luciferase construct. This method has broad utility for transfection of other cell types that are resistant to transfection.

3T3 Cells↗
PubMed1999

Antibodies to oxidized LDL predict coronary artery disease in type 1 diabetes: a nested case-control study from the Pittsburgh Epidemiology of Diabetes Complications Study.

The pathogenesis of excess cardiovascular risk in type 1 diabetes is unclear. LDL cholesterol is only weakly predictive, and its concentration is often normal in type 1 diabetes. We therefore examined whether markers of LDL oxidation such as antibodies to oxidized LDL (Ab-OxLDL) and LDL-containing immune complexes, rather than LDL concentration, were predictive of coronary artery disease (CAD) in type 1 diabetes. This nested case-control study from an epidemiologic cohort study included 49 incident cases of myocardial infarction (MI), angina, or CAD death and 49 age-, sex-, and duration-matched control subjects. Ab-OxLDL was measured by enzyme immunoassay and the apolipoprotein B (ApoB) content of immune complexes (ApoB-IC) precipitated by polyethylene glycol by immunoelectrophoresis in baseline stored samples. Ab-OxLDL was inversely, and ApoB-IC directly, related to subsequent CAD. In multivariate analyses, Ab-OxLDL remained a significant independent predictor along with previously recognized predictors, hypertension and Beck depression score. In conclusion, oxidation of LDL and the immune response it elicits may play a role in predicting the development of CAD in type 1 diabetes and explain at least some of the enhanced CAD risk in type I diabetes.

Adult↗
PubMed1998

Combined analysis of GAD65 and ICA512(IA-2) autoantibodies in organ and non-organ-specific autoimmune diseases confers high specificity for insulin-dependent diabetes mellitus.

There is evidence that insulin-dependent diabetes mellitus (IDDM) may develop in association with other non-beta-cell-specific autoimmune diseases. We aimed to assess whether autoantibodies to the islet cell antigens glutamic acid decarboxylase (Mr 65,000 isoform) (GAD65) and ICA512(IA-2), present alone or in combination, are limited to IDDM or also occur in other organ- or non-organ-specific autoimmune disorders. We determined the frequency of these autoantibodies by radioimmunoassay in 199 sera from patients with autoimmune thyroid diseases (AITD), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC), and compared the results with those from 507 newly diagnosed patients with IDDM and 280 healthy controls. ICA512(IA-2) autoantibodies were detected exclusively in AITD with concurrent IDDM, but not in other autoimmune diseases without IDDM, whereas GAD65 autoantibodies exceeded the limit of normal in 67.7% (21 of 31) of patients with AITD who also had IDDM and in 5.5% (three of 55) of patients with PBC. The frequency of either GAD65 and/or ICA512(IA-2) autoantibodies was significantly higher in patients with AITD who also had IDDM (27 of 31, 87.1%) than in those with AITD alone (one of 53, 1.9%; P<10(-6)), but was not significantly different from those patients with newly diagnosed IDDM (418 of 507, 82.4%). Neither patients with organ- or non-organ-specific autoimmune diseases without IDDM nor healthy controls had autoantibodies against both GAD65 and ICA512(IA-2). Despite the fact that one of the two autoantibodies was occasionally detected in patients with non-beta-cell-specific autoimmune diseases without IDDM, combined determination of GAD65 and ICA512(IA-2) autoantibodies specifically identified IDDM in the majority of patients with AITD. In conclusion, because of the strong association of IDDM with AITD, testing for multiple islet autoanti-bodies could be useful as a predictive marker for risk of progression to IDDM onset amongst patients with autoimmune thyroid disorders.

Adolescent↗
PubMed1998

The association between a family history of type 2 diabetes and coronary artery disease in a type 1 diabetes population.

OBJECTIVE: To examine whether a potential marker for type 2 diabetes (family history) is related to CAD in type 1 diabetic subjects. The two major types of primary diabetes, type 1 and type 2, are both associated with an increased risk of developing coronary artery disease (CAD). However, the etiology and associated risk factors may differ by type of diabetes. In type 2 diabetes, CAD is likely to be linked with the insulin resistance associated with the type 2 "process," while CAD in type 1 diabetes has, so far, been more closely linked to renal disease. Because the etiologies of type 1 and type 2 diabetes are different, it is possible that some CAD in type 1 diabetes may be related to the coexistence of type 2 diabetes susceptibility (i.e., insulin resistance). RESEARCH DESIGN AND METHODS: We evaluated the interrelationships between family history of type 2 diabetes (age at onset > 30 years, no insulin for 1st year) and presence of CAD in a cohort of childhood-onset type 1 diabetic subjects using the Pittsburgh Epidemiology of Diabetes Complications study (n = 658). RESULTS: A first-degree family history of type 2 diabetes was reported in 112 subjects, and CAD was present in 119 subjects. Those subjects reporting a family history of type 2 diabetes were significantly older, had a longer duration of type 1 diabetes, had higher triglyceride and LDL cholesterol levels, and had a borderline significantly increased Beck depression inventory. Sex differences in CAD risk factors were also noted. Using logistic regression analysis, the odds ratio (95% CI) for the presence of CAD in association with a family history of NIDDM was 1.89 (1.27-2.84). The odds ratio (95% CI) after adjusting for disease duration, triglycerides, hypertension, Beck depression, and nephropathy status was 1.45 (0.87-2.28). CONCLUSIONS: We conclude that a family history of type 2 diabetes is a risk factor for CAD in type 1 diabetic subjects. This supports the concept that insulin resistance may contribute to development of CAD in type 1 diabetes.

Adult↗
PubMed1997

Cumulative glycemic exposure and microvascular complications in insulin-dependent diabetes mellitus. The glycemic threshold revisited.

BACKGROUND: The development of microvascular insulin-dependent diabetes mellitus (IDDM) complications has been shown to be related to both duration of diabetes and the degree of glycemic exposure. However, controversy exists as to whether there is a threshold of glycemic exposure, below which there is minimal risk. Furthermore, there are few data describing the relationship of total glycemic exposure (duration x degree) to complications rates-a potentially useful research and clinical tool. OBJECTIVES: To determine a cumulative glycemic exposure variable that combines the effect of both degree and duration of hyperglycemia and to evaluate this variable in terms of its relation to microvascular complications. The association between cumulative glycemic exposure and complication risk was also examined to evaluate whether there was a threshold effect. METHODS: A total of 353 patients with IDDM who had completed the first 6 years of follow-up in the Pittsburgh Epidemiology of Diabetes Complications Study were included in this analysis. These subjects had a mean age of 27.9 years, and the mean duration of the disease was 19.4 years. Subjects were examined at baseline (cycle 1) and then biennially (cycle 2, cycle 3, and cycle 4) for diabetes complications. Total glycosylated hemoglobin (HbA1) was measured at each cycle. A cumulative glycemic exposure variable, named A1months, was calculated by multiplying the number of HbA1 units above normal at each cycle by the number of months between the midpoints of the preceding and succeeding cycle intervals. RESULTS: The mean number of A1months experienced at the time of diagnosis of proliferative retinopathy (914), microalbuminuria (952), overt nephropathy (1043), and distal symmetrical polyneuropathy (1043) did not vary by duration of diabetes. Thus, approximately 1000 A1months were needed (on average) for the advanced complications to develop. Although the risk for developing proliferative retinopathy rose gradually as A1months increased, a more abrupt increase in the risk was seen (again at approximately 1000 A1months) for microalbuminuria (odds ratio, 6.9; 95% confidence interval, 2.5-19.1), overt nephropathy (odds ratio, 6.5; 95% confidence interval, 2.0-21.7), and distal symmetrical polyneuropathy (odds ratio, 6.5; 95% confidence interval, 2.4-17.8). Nonetheless, complications developed in the majority of cases at glycemic exposures below 1000 A1months. The cumulative glycemic exposure variable A1months does not predict complications any better than its component variables (duration and HbA1). Furthermore, formal statistical testing failed to show a definitive threshold for any complication. CONCLUSIONS: Although A1months does not enhance prediction of complications, it may be a useful summary measure of glycemic exposure for both patients and physicians. However, although subjects with 1000 A1months or more appear to be at increased risk of developing most microvascular complications, because the majority of complications arise in subjects with less than this exposure, this threshold value should only be considered a minimal goal. For example, our data suggest that for most microvascular complications to develop, it would take, on average, 83 years with an HbA1 unit at 1% above normal, 42 years at 2% above normal, 28 years at 3% above normal. 21 years at 4% above normal, and 18 years at 5% above normal.

Adolescent↗
PubMed1997

Developmental and nutritional changes of ob and PPAR gamma 2 gene expression in rat white adipose tissue.

The ob gene encodes leptin, a hormone which induces satiety and increases energy expenditure. The peroxisome proliferator-activated receptor gamma 2 isoform (PPAR gamma 2) gene encodes a transcription factor which controls adipocyte differentiation and expression of fat-specific genes. We have studied the regulation of these two genes in white adipose tissue (WAT) during the suckling-weaning transition. Suckling rats ingest a high-fat diet (milk). Fat-pad weight barely varied during the last week of suckling. ob mRNA levels, which were very low in 15-day-old rats, rose approximately 6-fold until weaning at 21 days. When the rats were weaned on to a standard (high-carbohydrate) laboratory chow, epididymal WAT enlarged approximately 7-fold, and ob mRNA kept increasing progressively and doubled between 21 and 30 days. This evolution contrasted with that of fatty acid synthase (FAS) mRNA, which increased sharply, but only after weaning. To distinguish between the influence of developmental and nutritional factors on ob expression, a group of rats was weaned on to a high-fat diet. This prevented the rise in glycaemia and insulinaemia and the decrease in plasma non-esterified fatty acids which otherwise occurred at weaning. This also resulted in a slight (10-15%) decrease in food intake and body weight gain. Under this high-fat diet, the rise of ob mRNA in WAT was augmented (3.7-fold in 30- versus 21-day-old pups), whereas the normal rise in FAS mRNA levels was attenuated. Fat-pad weights and adipocyte cell size and number were roughly similar in high-carbohydrate- and high-fat-weaned pups. mRNA levels of PPAR gamma 2, like those of ob, were low in the WAT of 15-day-old suckling pups, doubled at 21 days, and reached a maximum as soon as 23 days. This evolution further differed from that of ob mRNA in not being influenced by diet composition. In conclusion, ob expression markedly increases during the suckling-weaning transition, and this effect is accentuated by a high-fat diet. Qualitative nutritional changes in ob mRNA were correlated with neither acute changes in adipose-tissue mass, nor cell size/number, nor variations in insulinaemia. PPAR gamma 2 also increased during suckling, but rapidly reached a plateau after weaning and no longer changed thereafter. Unlike ob, PPAR gamma 2 was not influenced by the diet composition.

Adipose Tissue↗
PubMed1997

Improvement of glucose homeostasis and hepatic insulin resistance in ob/ob mice given oral molybdate.

Molybdate (Mo) exerts insulinomimetic effects in vitro. In this study, we evaluated whether Mo can improve glucose homeostasis in genetically obese, insulin-resistant ob/ob mice. Oral administration of Mo (174 mg/kg molybdenum element) for 7 weeks did not affect body weight, but decreased the hyperglycaemia (approximately 20 mM) of obese mice to the levels of lean (L) (+/+) mice, and reduced the hyperinsulinaemia to one-sixth of pretreatment levels. Tolerance to oral glucose was improved: total glucose area was 30% lower in Mo-treated mice than in untreated ob/ob mice (O), while the total insulin area was halved. Hepatic glucokinase (GK) mRNA level and activity were unchanged in O mice compared with L mice, but the mRNA level and activity of L-type pyruvate kinase (L-PK) were increased in O mice by 3.5- and 1.7-fold respectively. Mo treatment increased GK mRNA levels and activity (by approximately 2.2-fold and 61% compared with O values), and had no, or only a mild, effect on the already increased L-PK variables. mRNA levels and activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK) were augmented in O liver (sixfold and by 57% respectively), and these were reduced by Mo treatment. Insulin binding to partially purified receptors from liver was reduced in O mice and restored by Mo treatment. Despite this correction, overall receptor tyrosine kinase activity was not improved in Mo mice. Moreover, the overexpression (by two- to fourfold) of the cytokine tumour necrosis factor alpha (TNF alpha) in white adipose tissue, which may have a determinant role in the insulin resistance of the O mice, was unaffected by Mo. Likewise, overexpression of the ob gene in white adipose tissue was unchanged by Mo. In conclusion, Mo markedly improved glucose homeostasis in the ob/ob mice by an insulin-like action which appeared to be exerted distal to the insulin receptor tyrosine kinase step. The blood glucose-lowering effect of Mo was unrelated to over-expression of the TNF alpha and ob genes in O mice, but resulted at least in part from attenuation of liver insulin resistance by the reversal of pre-translational regulatory defects in these mice.

Adipose Tissue↗
PubMed1997

Hypertension as a risk factor for diabetic neuropathy: a prospective study.

The pathogeneses of diabetic neuropathy is still unclear. This study prospectively investigated the risk factors for distal symmetrical polyneuropathy (DSP) in a cohort of childhood-onset IDDM patients. Subjects from the Epidemiology of Diabetes Complications (EDC) Study were clinically examined at baseline and then biennially. DSP was diagnosed by a combination of clinical criteria, symptoms and signs (Diabetes Control and Complications Trial [DCCT] exam), and quantitative sensory threshold (QST). Among the 463 (70.4%) subjects who were free of DSP at baseline, 453 (97.8%) participated in at least one biennial reexamination during the first 6 years of follow-up and were included in the current analysis. A total of 68 (15.0%) subjects developed DSP in 6 years, giving a cumulative probability of 0.29. The Cox proportional hazards model shows that longer IDDM duration, hypertension, poor glycemic control, height, and smoking were all independent predictors of the incidence of DSP (all P < 0.0001, except for smoking for which P = 0.03). Hypertension showed the greatest impact on the development of DSP for individuals with either short or long IDDM duration. This study confirms some risk factors for DSP found in cross-sectional studies and suggests a strong relationship between hypertension and DSP. The results indicate that in addition to good glycemic control, avoidance of smoking and good blood pressure control may be helpful in preventing or delaying the onset of DSP in IDDM patients.

Adolescent↗
PubMed1997

Health insurance and the financial impact of IDDM in families with a child with IDDM.

OBJECTIVE: To examine the health insurance experience and out-of-pocket health care costs of families with a child with IDDM. RESEARCH DESIGN AND METHODS: A case-control study of 197 families with a child with IDDM and 142 control families with no diabetic children was conducted. IDDM-affected families were identified from the Allegheny County IDDM Registry. Brothers and sisters of the parents in the IDDM-affected families were asked to participate as control subjects. Health insurance coverage and the money that families spent on health care services and supplies not reimbursed by insurance (out-of-pocket costs) were assessed by questionnaire. RESULTS: No difference was found between the IDDM-affected and control families in the percentages with or without insurance. Families with low household incomes ($10,000-$19,999) were at the greatest risk for having no insurance. While coverage provided by private plans was similar between the IDDM-affected and control families, many families had no reimbursement for insulin (10%), syringes (10%), or blood testing strips (30%). Out-of-pocket expenses were 56% higher in the IDDM-affected families than in the control families. Seventeen percent of the IDDM-affected families had expenses over 10% of their household income. This particularly affected families with low household incomes. Pre-existing illness clauses and insurance denial affected only a small proportion of the case families. CONCLUSIONS: These data illustrate that most families with a child with IDDM have health insurance, yet still incur larger out-of-pocket health care costs than do families without the presence of diabetes. IDDM-affected families likely face a number of economic decisions regarding health insurance and the use of health care.

Adolescent↗
PubMed1996

Oral selenate improves glucose homeostasis and partly reverses abnormal expression of liver glycolytic and gluconeogenic enzymes in diabetic rats.

Selenium is a trace element that exerts certain insulin-like actions in vitro. In this study, we evaluated its in vivo effects on the glucose homeostasis of rats made diabetic and insulin-deficient by streptozotocin. Na2SeO4 was administered ad libitum in drinking water and/or food for 10 weeks. The elevated plasma glucose levels (approximately 25 mmol/l) and glucosuria (approximately 85 mmol/day) of untreated rats were decreased by 50 and 80%, respectively, by selenate treatment. The beneficial effect of selenate was also evident during oral and intravenous glucose tolerance tests: the integrated glucose responses were decreased by 40-50% as compared to those in untreated rats. These effects were not due to an increase in plasma insulin levels. Compared to non-diabetic rats, pancreatic insulin reserves were reduced by more than 90% in treated and untreated diabetic rats. The hepatic activities and mRNA levels of two key glycolytic enzymes, glucokinase and L-type pyruvate kinase were blunted in diabetic rats. They increased approximately two- to threefold after selenate treatment, to reach 40-75% of the values in non-diabetic rats. In contrast, elevated activity and mRNA levels of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase, were reduced by 40-65% after selenate administration. Since selenate induced a moderate decrease in body weight due to an anorexigenic effect, we checked that there was no improvement of glucose homeostasis or hepatic glucose metabolism in an additional group of calorie-restricted diabetic rats, which was weight-matched with the selenate group. In addition, no obvious toxic side-effects on the kidney or liver were observed in the rats receiving selenate. In conclusion, selenate induces a sustained improvement of glucose homeostasis in streptozotocin-diabetic rats by an insulin-like action, which involves partial correction of altered pretranslational regulatory mechanisms in liver metabolism.

Administration, Oral↗
PubMed1996

The changing course of diabetic nephropathy: low-density lipoprotein cholesterol and blood pressure correlate with regression of proteinuria.

Diabetic nephropathy (DN) as manifested by persistent and clinically evident proteinuria, has long been considered an irreversible process that predicts a rapid decline in renal function. The observation of reversal of DN in several individuals enrolled in a prospective study of the natural course of diabetes complications challenged this view and led to the current investigation into the correlates of such regression of proteinuria. DN was defined as a median albumin excretion rate (AER) over 200 microg/min in two or three urine collections obtained at baseline, and again at 2 and 4 years of follow-up. Among 658 individuals with childhood-onset insulin-dependent diabetes mellitus (IDDM), 146 had DN at baseline. Nine subsequently died without renal failure, and 13 were lost to follow-up. Of the 124 subjects with at least survey follow-up data, 32 (24%) developed renal failure, and 78 of the remaining 92 provided full quantitative data. AER decreased by > or = 10-fold into the microalbuminuric (20 to 200 microg/min) or normal range (<20 microg/min) in 7 of these individuals and are called "regressors of proteinuria." Compared with the remaining 71 subjects, the strongest correlate of regression of proteinuria was an improvement in fasting plasma low-density lipoprotein cholesterol (LDL-C) in the 7 regressors (P < 0.008). Improved glycemic control was not a significant predictor of improved AER. Five of the 7 individuals with improved AER had a baseline median AER below 500 microg/min. When the 7 regressors of proteinuria were combined with an additional 38 individuals who also experienced smaller decreases in median AER, such improvement was associated with a more favorable systolic (or diastolic) blood pressure (BP) change (P < 0.01), and a decrease in plasma LDL-C level (P = 0.01). These data suggest that proteinuria in DN may substantially regress in approximately 6% and improve in at least 34% of individuals with IDDM over a 4-year period, often in association with a decrease in plasma LDL-C concentration or stabilization or improvement in BP. Furthermore, the data suggest that the nonreversibility threshold for diabetic nephropathy may be higher (500 mg/min) than previously reported (200 microg/min).

Adult↗
PubMed1996

Improvement of glucose and lipid metabolism in diabetic rats treated with molybdate.

Molybdenum mimics certain insulin actions in vitro. We have investigated the effects of oral administration of Na2MoO4 (Mo) for 8 wk on carbohydrate and lipid metabolism in streptozotocin-diabetic rats. Mo decreased hyperglycemia and glucosuria by 75% and corrected the elevation of plasma nonesterified fatty acids. Tolerance to glucose loads was improved, and glycogen stores were replenished. These effects were not due to a rise of insulinemia. In liver, Mo restored the blunted mRNA and activity of glucokinase and pyruvate kinase and decreased to normal phosphoenolpyruvate carboxykinase values. Finally, Mo totally reversed the low expression and activity of acetyl-CoA carboxylase and fatty acid synthase in liver, but not in white adipose tissue. In conclusion, Mo exerts a marked blood glucose-lowering effect in diabetic rats by an insulin-like action. This effect results in part from a restoration of hepatic glucose metabolism and is associated with a tissue-specific correction of lipogenic enzyme gene expression, both processes being essentially mediated by reversal of impaired pretranslational regulatory mechanisms. These observations raise new therapeutic perspectives in diabetes, particularly in the insulin-resistant condition.

Animals↗
PubMed1996

Coronary artery disease in IDDM. Gender differences in risk factors but not risk.

Insulin-dependent diabetes mellitus (IDDM) increases the risk of developing coronary artery disease (CAD) compared with that seen in the general population, while the sex differential in rates of CAD is considerably reduced in IDDM populations. To further our understanding of these observations, the effects of gender on baseline risk factors for CAD incidence were examined. Participants in the Pittsburgh Epidemiology of Diabetes Complications (EDC) Study were recruited from the Children's Hospital of Pittsburgh IDDM registry and had been diagnosed between 1950 and 1980. Subjects completed a series of questionnaires and were given a full clinical examination at baseline (1986 through 1988) and every subsequent 2 years. This report is based on the first 4 years of follow-up. Similar incidence rates of new CAD events were observed in men and women. In neither sex was glycemic control a predictor of later CAD. Sex-specific Cox proportional hazards models showed that for men, duration of IDDM, HDL cholesterol, fibrinogen, hypertension, and smoking were all significantly associated with the onset of CAD. Hypertension, fibrinogen, and smoking were all replaced by nephropathy when this latter variable was added to the model. For women, duration, hypertension, waist-hip ratio, physical activity, and depressive symptomatology were all significant independent predictors of CAD. Nephropathy status did not enter the model for women. While 4-year incidence of CAD in IDDM varies little by sex in this population, the predictive risk factors vary considerably. In particular, the effect of renal disease was stronger in men, while the cluster of physical activity, waist-to-hip ratio, and depressive symptomatology were more important in women. These results may help explain the relatively greater impact IDDM has on CAD risk for women and suggest new potential preventive approaches.

Adolescent↗
PubMed1996

The dietary intake of children with IDDM.

OBJECTIVE: To assess the dietary intake of children with IDDM and to determine whether the intake meets the current nutritional recommendations for children with IDDM. RESEARCH DESIGN AND METHODS: A total of 66 children with IDDM who were < 10 years of age were recruited from two suburban Pennsylvania hospitals. To collect dietary intake data, subjects were asked, via telephone interview, to complete three random-day 24-h dietary recalls. Data were analyzed for the content of nutrients and other food components by a computerized database program. Intakes were expressed as a 3-day average intake for each subject. RESULTS: Overall mean intake of protein and cholesterol approximated the current recommendations. The mean intake of saturated fat exceeded recommendations, while fiber intake was less than the recommended level. Many of the children consumed levels of saturated fat well above recommendations. Energy, vitamin, and mineral intakes were adequate for the overall sample. However, from 10 to 40% of the sample had an inadequate intake of vitamin D, vitamin E, and zinc. The percentage of those with inadequate intakes of these nutrients decreased with age. CONCLUSIONS: These data suggest that, on average, among this sample of children with IDDM aged < 10 years, adherence to the current nutritional recommendations for children with IDDM was adequate, but some individual children had intakes that were not consistent with the recommendations for optimal management of IDDM.

Child↗
PubMed1995

Diet- and diabetes-induced changes of ob gene expression in rat adipose tissue.

ob gene regulation is as yet unknown. We first examined whether the ob gene is under physiological control by the nutritional state. Fasting produced a sharp (95%) decrease of ob mRNA in epididymal and inguinal fat pads from 24 h onward. Refeeding rapidly (3-6 h) re-induced ob gene expression and corrected it within 24 h. Similar changes in fatty acid synthase (FAS) and GLUT4 mRNAs were observed, whereas phosphoenolpyruvate carboxykinase (PEPCK) mRNA showed an opposite evolution. We next examined the potential role of insulin. In adipose tissue of streptozotocin-diabetic rats, ob mRNA levels were decreased by 80%. Insulin treatment (4 days) only marginally increased ob mRNA, but restored euglycemia and overcorrected FAS, GLUT4 and PEPCK expression. In conclusion, we provide evidence for a physiological regulation of ob gene by variations in the nutritional state. We also show that ob expression is impaired in streptozotocin-diabetic rats and only slightly restored by insulin treatment, which suggests that ob gene is not or only minimally regulated by the hormone.

Adipose Tissue↗
PubMed1995

Regional cerebral blood flow during hypoglycaemia in children with IDDM.

Hypoglycaemia may cause transient cognitive impairment and neurological deficits that are frequently unilateral. The effect of mild hypoglycaemia (serum glucose level 3.4 +/- 0.1 mmol/l; mean +/- SEM) on regional cerebral blood flow and cerebrovascular resistance was studied in eight right-handed children with insulin-dependent diabetes mellitus (age 14.9 +/- 0.7 years; diabetes duration 7.4 +/- 1.1 years; six males) using the intravenous xenon-133 clearance method. Global mean cerebral grey and white matter blood flow, adjusted to mean pCO2 of cohort, showed a trend towards an increase from 54.7 +/- 3.5 ml.100 g-1.min-1 at baseline euglycaemia to 58.0 +/- 4.1 ml.100 g-1.min-1 during hypoglycaemia (p = 0.075). Statistically significant changes were seen in global mean cerebral grey matter blood flow, as indexed by initial slope, which increased from 88.0 +/- 6.5 min-1 before hypoglycaemia to 96.3 +/- 7.2 min-1 during hypoglycaemia (p < 0.05). Cerebral grey matter blood flow was significantly higher in the right hemisphere compared to the left during hypoglycaemia (p < 0.01) but not at baseline euglycaemia. Measurements of global cerebrovascular resistance showed a borderline decrease from 1.64 +/- 0.11 to 1.54 +/- 0.11 mm Hg.ml-1.100 g-1.min-1 (p < 0.09). In conclusion, mild hypoglycaemia is associated with increases in cerebral blood flow which are greater in grey matter flow indices and in the right hemisphere. We speculate that asymmetrical cerebral blood flow changes may explain the frequent laterality of neurological deficits during severe hypoglycaemia.

Adolescent↗