New adolescent polycystic ovary syndrome perspectives.

Polycystic ovary syndrome (PCOS) is a common but heterogeneous disorder that usually arises during puberty. This endocrine disorder is associated with chronic anovulation and hyperandrogenemia with clinical manifestation of oligomenorrhea, hirsutism and acne. While the underlying etiology of PCOS remains unknown, it is commonly associated with obesity and insulin resistance leading to increased risk of cardiovascular disease, dyslipidemia and type 2 diabetes mellitus in hyperandrogenemic phenotypes. Menstrual irregularities and insulin resistance in obese adolescents are usually indistinguishable from the clinical manifestations of PCOS and pose a diagnostic dilemma due to higher circulating androgens during puberty. Consequently, a universal consensus on the definition of hyperandrogenemia in adolescents has been elusive. Nevertheless, hyperandrogenemia, independent of obesity, in postmenarchal adolescents is associated with increased risk of cardiometabolic syndrome. Therefore, treatment strategies including lifestyle changes and/or use of insulin-sensitizers, hormone replacement and antiandrogens should be utilized in order to delay long-term cardiovascular and metabolic complications of this endocrinopathy.

Genetic association of HLA DQB1 with CD4+CD25+(high) T-cell apoptosis in type 1 diabetes.

Type 1 diabetes (T1D) has a strong genetic component and the major locus lies in the HLA DQB1 region. We found earlier an increased apoptosis with decreased viability and function of the CD4+CD25+(high) T-cell subset (Treg) in human subjects with recent-onset T1D and in multiple autoantibody-positive, high at-risk individuals. Tregs normally inhibit or delay onset of T1D in animal models and increased Treg apoptosis could bring on or accelerate disease from effector T-cell-mediated destruction of insulin-producing beta cells. In this study, we test the hypothesis that HLA DQB1 genotypes are associated with increased CD4+CD25+(high) T-cell apoptosis. HLA DQ-based genetic risk status was significantly associated with CD4+CD25+(high) T-cell apoptosis, after adjustment for age, gender and phenotypic status (n=83, F=4.04 (d.f.=3), P=0.01). Unaffected, autoantibody-negative high risk HLA DQB1 control subjects showed increased CD4+CD25+(high) apoptosis levels compared with low risk HLA DQB1 control subjects (n=26, P=0.002), confirming that the association precedes disease. The association of specific HLA DQB1 genotypes with Treg apoptosis was also tested, showing significance for HLA DQB1*0302, DQB1*0201 and HLA DQB1*0602 alleles. Our study shows an association of HLA DQB1 genotypes with CD4+CD25+(high) T-cell apoptosis, which implicates CD4+CD25+(high) T-cell apoptosis as a new intermediate trait for T1D.

Dynamic changes in CD4+ CD25+(high) T cell apoptosis after the diagnosis of type 1 diabetes.

Because type 1 diabetes (T1D) is a chronic, autoimmune, T cell-mediated disease, interventions affecting T cells are expected to modulate the immune cascade and lead to disease remission. We propose that increased CD4(+) CD25(+high) T cell apoptosis, a trait we discovered in recent-onset T1D subjects, reflects T1D partial remission within the first 6 months after diagnosis. Apoptosis of forkhead box P3 (FoxP3)(+) CD4(+) CD25(+high) T cells, in addition to total daily doses of insulin (TDD), blood glucose, HbA1c and age, were measured in 45 subjects with T1D at various times after diagnosis. Sixteen healthy control subjects were also recruited to the study. Higher CD4(+) CD25(+high) T cell apoptosis levels were detected within the first 6 months of diagnosis (odds ratio = 1.39, P = 0.009), after adjustment for age, TDD and HbA1c. A proportional hazards model confirmed that the decline of apoptosis after diagnosis of T1D was related significantly to survival time (hazards ratio = 1.08, P = 0.014), with TDD and age also contributing to survival. During this time there was an inverse relationship between CD4(+) CD25(+high) T cell apoptosis with TDD (r = -0.39, P = 0.008). The CD4(+) CD25(+high) T cell apoptosis levels decline significantly after the first 6 months from diagnosis of T1D and may help in the close monitoring of autoimmunity. In parallel, there is an increase in TDD during this time. We also propose that CD4(+) CD25(+high) T cell apoptosis assay can be used to gauge the efficacy of the several immune tolerance induction protocols, now under way.

Beneficial effects of flexible insulin therapy in children and adolescents with type 1 diabetes mellitus.

The purpose of this study was to determine the feasibility of a flexible multiple daily insulin (FMDI) regimen in routine pediatric diabetes care by comparing HbA(1c), body mass index (BMI), and episodes of severe hypoglycemia (SH) before and after initiation of FMDI therapy. Data from 44 patients (2-16 years old), on a conventional insulin (CI) regimen, were collected during quarterly diabetes clinic visits. These patients were transitioned from CI to FMDI regimen: pre-meal lispro (bolus) and once or twice daily Humulin Ultralente with or without bedtime Humulin NPH as the basal insulin. There was a significant improvement in HbA(1c) in prepubertal (9.3%+/-1.3% vs. 8.0%+/-1.1%, p<0.002) and pubertal subjects (9.2%+/-1.0% vs. 8.2%+/-0.9%, p<0.001). Pubertal subgroup demonstrated an increase in BMI (21.3+/-3.1 vs. 22.7+/-3.2 kg/m(2), p<0.0001) after one year. The rate of SH was decreased in both prepubertal ( p<0.01) and pubertal ( p<0.05) groups of patients on FMDI therapy. The use of FMDI in a general pediatric diabetic population is a feasible therapeutic option for maintenance and possible improvement of glycemic control. It may effectively decrease the HbA(1c), and reduce hypoglycemic episodes, without producing an abnormal increase in BMI.

Beneficial effects of metformin in normoglycemic morbidly obese adolescents.

Hyperinsulinemia and insulin resistance are common features of obesity in humans and experimental animals. It has been demonstrated that metformin, an antihyperglycemic agent, decreases hyperinsulinemia and insulin resistance leading to decreased adiposity in obese and non-insulin-dependent diabetes mellitus (NIDDM) adults. To evaluate the antiobesity effect of metformin, we conducted a randomized double-blind placebo controlled trial in 24 hyperinsulinemic nondiabetic obese adolescents (body mass index [BMI] >30 kg/m(2)). All subjects were placed on a low-calorie (1,500 kcal for women and 1,800 kcal for men) meal plan. After an initial 1-week lead-in period, 12 subjects (mean +/- SE for age and BMI, 15.6 +/- 0.4 and 41.2 +/- 1.8, respectively) received metformin (850 mg twice daily) for 8 weeks, and 12 subjects (mean +/- SE for age and BMI, 15.7 +/- 0.5 and 40.8 +/- 1.4, respectively) received placebo. Compared to the placebo group, the metformin group had greater weight loss (6.5% +/- 0.8% v 3.8 +/- 0.4%, P <.01), greater decrease in body fat (P <.001), greater increase in fat-free mass to body fat ratio (P <.005), and greater attenuation of area under the curve (AUC) insulin response to an oral glucose tolerance test (P <.001). This was associated with enhanced insulin sensitivity, as determined by the fasting plasma glucose:insulin, 2-hour glucose:insulin, and AUC glucose:AUC insulin ratios, in the metformin group compared to controls (P <.01). This corresponded to a significant reduction in plasma leptin (P <.005), cholesterol, triglycerides, and free fatty acid (FFA) levels (P <.05) only in the metformin-treated subjects. Combined metformin treatment and low-calorie diet had a significant antiobesity effect in hyperinsulinemic obese adolescents compared to a low-calorie diet alone.

Diazoxide effects on hypothalamic and extra-hypothalamic NPY content in Zucker rats.

To determine if the anorectic effects of the insulin antagonist diazoxide (DZ) are mediated by reduced central neuropeptide Y (NPY), female Zucker rats, given DZ (150 mg/kg/day) or placebo for about four weeks, were sacrificed following overnight fasting or free feeding. Several hypothalamic and extra-hypothalamic nuclei were extracted for NPY content. DZ reduced weight gain in obese rats and lowered glucose of lean and obese rats without affecting insulin. Contrary to the hypothesis, DZ increased NPY in hypothalamic nuclei of free fed lean and obese rats. DZ elevated hypothalamic NPY levels in fasted obese rats and had more diverse effects in extra-hypothalamic nuclei of lean rats.

Diazoxide down-regulates leptin and lipid metabolizing enzymes in adipose tissue of Zucker rats.

We have previously reported that attenuation of hyperinsulinemia by diazoxide (DZ), an inhibitor of glucose-mediated insulin secretion, increased insulin sensitivity and reduced body weight in obese Zucker rats. These findings prompted us to investigate the effects of DZ on key insulin-sensitive enzymes regulating adipose tissue metabolism, fatty acid synthase (FAS), and lipoprotein lipase (LPL), as well as on circulating levels of leptin. We also determined the direct effects of diazoxide on FAS in 3T3-L1 adipocytes. Seven-week-old female obese and lean Zucker rats were treated with DZ (150 mg/kg/d) or vehicle (C, control) for a period of 6 wk. Changes in plasma parameters by DZ include significant decreases in triglycerides, free fatty acids, glucose, and insulin, consistent with our previous reports. DZ obese rats exhibited lower plasma leptin levels (P<0.03) compared to their C animals. DZ significantly reduced adipose tissue FAS activity in both lean (P<0.0001) and obese (P<0.01) animals. LPL mRNA content was also decreased significantly in DZ-treated obese animals (P<0.009) as compared to their respective controls without a significant effect on lean animals. The possibility that DZ exerted a direct effect on adipocytes was further tested in cultured 3T3-L1 adipocytes. Although diazoxide (5 microM) alone did not change FAS activity in cultured 3T3-L1 adipocytes, it significantly attenuated insulin's effect on FAS activity (P<0.001). We demonstrate that DZ regulates key insulin-sensitive enzymes involved in regulation of adipose tissue metabolism. These findings suggest that modification of insulin-sensitive pathways can be therapeutically beneficial in obesity management.

Effect of diazoxide on brain capillary insulin receptor binding and food intake in hyperphagic obese Zucker rats.

Insulin is believed to act as a central adiposity signal by binding to hypothalamic and other brain insulin receptors. Entry of circulating insulin into the brain is accomplished by a saturable receptor-mediated transendothelial transport system and is believed to be impaired in hyperinsulinemic, insulin-resistant, and hyperphagic obese Zucker rats. Theoretically, if hyperinsulinemia is decreased simultaneously while brain capillary insulin binding is increased, uptake of insulin into the brain can be enhanced leading to reduced food intake. To test this hypothesis, we administered diazoxide (DZ, 150 mg/kg/day), an inhibitor of glucose-mediated insulin secretion, or vehicle (control) to 7-week-old female obese and lean Zucker rats for 4 weeks (n = 24-28/subgroup-strain). Animals were assigned to either fasted (FD) or free-fed (FF) protocol for determination of plasma and cerebrospinal fluid (CSF) insulin and brain capillary insulin binding at the end of 4 weeks. DZ obese consumed fewer calories (P<0.01) and gained less weight than control obese (P<0.01), whereas DZ lean had similar amounts of caloric intake and weight gain compared with lean controls. DZ obese had lower fasting and random plasma glucose than control obese (P<0.05). FD and FF DZ-treated obese and lean rats had lower plasma insulin than their respective obese (P<0.01) and lean (P<0.01) controls. FD and FF DZ-treated obese rats demonstrated higher CSF insulin (P<0.05) and CSF/ plasma insulin ratio (P<0.01) than their controls, while only FF DZ lean animals showed higher CSF/plasma insulin ratio (P<0.01) than their controls (P<0.05). This was associated with enhanced brain capillary insulin binding in FD and FF DZ-treated obese (P<0.01) and lean (P<0.05) animals compared with their respective controls. It was concluded that DZ treatment in obese Zucker rats caused a decrease in insulin secretion and partially reversed impaired insulin binding to brain capillaries, leading to enhanced brain insulin uptake, and resulted in reduced food intake and weight gain observed in these animals.

Anabolic effects of growth hormone treatment in young children with cystic fibrosis.

BACKGROUND: Malnutrition is commonly found in children with Cystic Fibrosis (CF) and is characterized by poor weight gain and linear growth. Almost one-third of children with CF are below 5th percentile for weight and height. Intensive nutritional supplementation may not result in sustained improvement in weight gain and linear growth. OBJECTIVE: To evaluate the anabolic effects of GH, Humatrope (Eli Lilly, 0.05 mg/kg/day) was administered to five children with CF (3 males/2 females) for an average period of 2 years. METHODS: All patients were maintained on caloric intake of 1.3-2.0 times the recommended daily allowance. Patients underwent standard growth hormone (GH) stimulation studies and measurement of IGF-1 and IGFBP-3. RESULTS: The mean +/- SE for age and skeletal age were 3.2 +/- 0.85 years and 2.0 +/- 0.45 years, respectively. Growth was assessed by determining both weight and height, which were normalized for age and sex by calculating Z scores using HANES I reference data. Differences in Z scores between clinic visits (delta Z) were calculated for both weight and height to determine changes in growth velocity. The mean Z scores for weight and height were markedly attenuated in CF children as compared with healthy children (-1.95 +/- 0.23 and -2.8 +/- 0.27, respectively). The mean +/- SE for maximum stimulated GH value, IGF-1 and IGFBP-3 were 9.2 +/- 1.2 ng/dl, 67 +/- 6 ng/ml, and 1.7 +/- 0.22 mg/L, respectively. GH treatment improved weight and height Z scores (-0.11 +/- 0.05 and -0.94 +/- 0.18, p < 0.01) significantly. The delta Z scores for weight and height were significantly increased during first and second year of GH treatment (p < 0.02). Also, the average values of IGF-1 and IGFBP-3 were significantly increased as compared to pretreatment values (186 +/- 37 ng/ml and 3.0 +/- 0.22 mg/L, p < 0.01). CONCLUSIONS: GH treatment significantly improves weight and linear growth in young patients with CF. These data suggest that anabolic effects of GH may be beneficial for treatment of malnutrition in children with CF.

Beneficial effect of diazoxide in obese hyperinsulinemic adults.

UNLABELLED: Hyperinsulinemia, insulin resistance, and increased adipose tissue are hallmarks of the obesity state in both humans and experimental animals. The role of hyperinsulinemia as a possible preceding event in the development of obesity has been proposed. We previously demonstrated that administration of diazoxide (DZ), an inhibitor of insulin secretion, to obese hyperinsulinemic Zucker rats resulted in less weight gain, enhanced insulin sensitivity, and improved glucose tolerance. Assuming that hyperinsulinemia plays a major role in the development of human obesity, then its reversal should have therapeutic potential. To test this hypothesis, we conducted a randomized placebo-controlled trial in 24 hyperinsulinemic adults [body mass index (BMI) > 30 kg/m2]. All subjects were placed on a low-calorie (1260 for females and 1570 for males) Optifast (Sandoz, Minneapolis, MN) diet. After an initial 1-week lead-in period, 12 subjects (mean +/- SE for age and BMI, 31 +/- 1 and 40 +/- 2, respectively) received DZ (2 mg/kg BW.day; maximum, 200 mg/day, divided into 3 doses) for 8 weeks; and 12 subjects (mean +/- SE for age an BMI, 28 +/- 1 and 43 +/- 1, respectively) received placebo. Compared with the placebo group, DZ subjects had greater weight loss (9.5 +/- 0.69% vs. 4.6 +/- 0.61%, P < 0.001), greater decrease in body fat (P < 0.01), greater increase in fat-free mass to body fat ratio (P < 0.01), and greater attenuation of acute insulin response to glucose (P < 0.01). However, there was no significant difference in insulin sensitivity and glucose effectiveness, as determined by the insulin-modified i.v. glucose tolerance test (Bergman's minimal model) and no significant difference in glycohemoglobin values. CONCLUSION: 8 weeks treatment with DZ had a significant antiobesity effect in hyperinsulinemic obese adults without inducing hyperglycemia.

Efficacy of low-dose dextromethorphan in the treatment of nonketotic hyperglycinemia.

Nonketotic hyperglycinemia (NKH) is an inborn error of glycine degradation causing muscular hypotonia, seizures, apnea, and lethargy; it has a poor prognosis. Accumulation of glycine in the brain is thought to cause excessive stimulation of the N-methyl-D-aspartate receptor. Dextromethorphan (DM), an N-methyl-D-aspartate receptor antagonist, in doses of 5 to 35 mg/kg per day has been shown to have beneficial therapeutic effects in some patients with NKH. We report the case of a 1-year-old infant with NKH, seizure disorder, and psychomotor delay who was clinically seizure free during treatment with sodium benzoate, arginine, benzodiazepam, and phenobarbital. Although sodium benzoate normalized serum glycine levels (103 to 125 mumol/L), cerebrospinal fluid glycine levels remained elevated (42 to 47 mumol/L), with epileptiform activity on electroencephalography. The addition of low-dose DM (0.25 mg/kg per day) to the treatment led to improvement of electroencephalographic activity, resolution of nystagmus with increased eye contact, and modest progression of developmental milestones. These data suggest that DM at doses significantly lower than previously reported may be beneficial in some patients with NKH. Treatment with low-dose DM needs further evaluation.

Antiobesity effect of diazoxide in obese Zucker rats.

Hyperinsulinism and insulin resistance are characteristic findings in obese subjects. Obesity in both humans and experimental animals is associated with a reduced number of insulin receptors and a decreased insulin-mediated glucose disposal, whereas sensitivity to insulin's antilipolytic action is unaltered. To evaluate the antiobesity effect of diazoxide (DZ), an inhibitor of glucose-stimulated insulin release, 7-week-old Zucker obese and lean rats were studied. Obese and lean rats were grouped into DZ-treated (150 mg/kg/d) and control (C) groups. DZ-treated obese rats consumed similar amounts of calories per kilogram body weight (BW) compared with C obese animals, but gained less weight (P<.01). Postabsorptive plasma free fatty acids (FFA), cholesterol, and triglycerides were significantly higher in obese versus lean animals (P<.01). DZ treatment reduced plasma triglyceride levels in obese animals (P<.001), but had no significant effect on FFA or cholesterol concentrations. Plasma glucose concentrations in the postabsorptive state and during glucose tolerance tests (GTTs) were significantly lower in DZ obese versus C obese rats (P<.01) despite a decrease in plasma insulin concentrations in DZ-treated animals (P<.01). In contrast, DZ lean rats developed glucose intolerance (P<.05). Sensitivity and responsiveness to the antilipolytic effect of insulin in isolated adipocytes were significantly decreased in DZ obese as compared with C obese rats (P<.01). Moreover, adipocyte specific insulin receptor binding was increased in both DZ lean and DZ obese animals (P<.01). This was accompanied by increased basal and insulin-stimulated glucose transport in both genotypes (P<.01). In conclusion, DZ increased insulin receptor binding and glucose transport while decreasing hyperinsulinemia and insulin sensitivity to the antilipolytic action of insulin. This combined effect resulted in improved glucose tolerance and a decrease in weight gain in obese rats, implying that pharmacologic modification of the disturbed insulin metabolism of obesity may be therapeutically beneficial.

Does glycemic control affect growth velocity in children with insulin-dependent diabetes mellitus.

To determine the effect of glycemic control on linear growth in children with insulin-dependent diabetes mellitus type 1, we studied 82 patients (40 male, 42 female) over a 6-year period. The mean +/-SD for age of onset and duration of IDDM were 7.3 +/- 3.9 years and 4.8 +/- 3.5 years, respectively. At each clinic visit, glycemic control was assessed by measuring glycosylated hemoglobin (GHb). For a total of 751 clinic visits, the mean +/- SD for chronologic age and GHb were 11.5 +/- 3.8 years and 10.2% +/- 2.3%, respectively. Good glycemic control was correlated with more frequent clinic visits (r= 0.219, P < 0.05). Growth was assessed by determining both weight and height, which were normalized for age and sex by calculating Z scores for weight and height and GHb. Moreover, regression analysis revealed no significant correlation between GHb levels and delta Z for either weight or height. While a significant correlation was observed between delta Z for weight and height (r = 0.30, P < 0.01), the relationship was not affected by glycemic control. Therefore, these data demonstrate that weight gain and growth rate do not seem to be significantly affected by glycemic control. This study also confirms that linear growth velocity is dependent on weight gain and suggests that in type 1 children, weight gain and level of growth-producing hormones such as insulin-like growth factor-1 (IGF-1) are more important regulators of linear growth than glycemic control.

Splicing mutation in CYP21 associated with delayed presentation of salt-wasting congenital adrenal hyperplasia.

Patients with salt-wasting congenital adrenal hyperplasia (SW-CAH) most commonly carry an A-G transition at nucleotide 656 (nt 656 A-->G), causing abnormal splicing of exons 2 and 3 in CYP21, the gene encoding active steroid 21-hydroxylase. Affected infants are severely deficient in cortisol and aldosterone, and usually come to medical attention during the neonatal period. We report on 2 affected boys, homozygous for the nt 656 mutation, who thrived in early infancy, but suffered salt-wasting crises unusually late in infancy, at 3.5 and 5.5 months, respectively. Laboratory studies at presentation showed hyponatremia, hyperkalemia, dehydration, and acidosis; serum aldosterone was low in spite of markedly elevated plasma renin activity. Basal 17-hydroxyprogesterone levels were only moderately elevated, yet the stimulated levels were more typical of severe, classic CAH due to 21-hydroxylase deficiency. Genomic DNA from the patients was analyzed. Southern blot showed no major deletions or rearrangements. CYP21-specific amplification by polymerase chain reaction, coupled with allele-specific hybridization using wild-type and mutant probes at each of 9 sites for recognized disease-causing mutations, revealed a single, homozygous mutation in each patient: nt 656 A-->G. These results were confirmed by sequence analysis. We conclude that the common nt 656 A-->G mutation is sometimes associated with delayed phenotypic expression of SW-CAH. We speculate that variable splicing of the mutant CYP21 may modify the clinical manifestations of this disease.

Modification of insulin resistance by diazoxide in obese Zucker rats.

Hyperinsulinism, insulin resistance, and decreased number of insulin receptors are characteristic of obesity in both humans and experimental animals. To assess the role of insulin in developing obesity, diazoxide (DZ), an inhibitor of glucose-stimulated insulin secretion, was administered for 8 weeks to 7-week-old female Zucker rats in two concentrations, 50 mg/kg.day (LD-DZ), and 100 mg/kg.day (HD-DZ). The obese and lean rats were divided into three subgroups: diazoxide (DZ), pair-fed (PF), and control (C) groups (n = 6 rats/subgroup-genotype). Diazoxide-treated obese and lean animals showed significantly lower postabsorptive plasma insulin concentrations (P < 0.005) than their respective obese and lean PF and C subgroups. HD-DZ obese rats consumed more calories (P < 0.001), yet gained less weight (P < 0.05) than PF and C rats. The plasma glucose concentrations in the postabsorptive state and during glucose tolerance tests in HD-DZ obese rats were significantly lower than those in PF and C rats (P < 0.01) despite a decrease in their plasma insulin concentrations (P < 0.01), whereas HD-DZ lean rats displayed a diabetic response (P < 0.01). The adipocyte-specific insulin receptor binding was dose-dependently increased in both lean and obese DZ animals (P < 0.01). DZ had a dual effect on insulin metabolism; it decreased insulin secretion and increased insulin receptor binding. This dual effect was associated with improved glucose tolerance and a decrease in weight gain in obese rats.

Is there compensated hypothyroidism in infancy?

The state-mandated newborn thyroid screening program may uncover infants who exhibit normal thyroxine (T4) levels with various degrees of hyperthyrotropinemia. To elucidate further the thyroid status, the basal metabolic rate (BMR) of 10 infants (7 boys, 3 girls; aged 9 to 63 days) was studied by indirect calorimetry. They were clinically euthyroid and healthy with no evidence of overt biochemical hypothyroidism (low T4, high thyroid-stimulating hormone [TSH]). Confirmatory testing indicated that all infants had normal serum T4 levels for age (mean +/- SD: 10.3 +/- 3.2 micrograms/dL). However, serum TSH levels varied from 2.3 to 99.2 microU/mL. In 4 infants (2 boys, 2 girls) the BMR was low (38.1 +/- 4.1 kcal/kg per day), while the other 6 patients (5 boys, 1 girl) demonstrated BMRs within the normal range (49.6 +/- 1.9 kcal/kg per day, P less than .001). The serum TSH levels were above 7.0 microU/mL among those infants with a low BMR, whereas the serum TSH levels were always below 6.0 microU/mL among the normometabolic infants. All infants who had a low BMR received thyroid therapy and promptly became normometabolic (BMR: 48.7 +/- 1.0 kcal/kg per day) with suppression of TSH levels (3.2 +/- 1.3 microU/mL) within 3 weeks of therapy, while their serum T4 levels remained within the normal range. The observed normalization of BMR in parallel to reduction of TSH levels following thyroid replacement therapy strongly suggests that these patients demonstrated a hypometabolic state, despite normal serum T4 levels. Therefore, the assessment of BMR may help define subclinical hypothyroidism in infancy in conjunction with a close monitoring of TSH concentration.

Reported dietary intakes of patients with insulin-dependent diabetes mellitus: limitations of dietary recall.

Reported dietary intakes were assessed in young patients with insulin-dependent diabetes mellitus (IDDM). We studied 44 IDDM patients (24 males, 20 females, mean +/- SD age 13.2 +/- 4.5 yr) and compared them with 44 healthy age- and sex-matched control subjects. Estimated intakes from 24-h dietary recall were analyzed in relation to body weight and degree of diabetes control. The reported energy intake of the IDDM patients with greater than 120% ideal body weight (IBW) for height was 66, 59/88% (where X = geometric mean, L1 = lower confidence limit/L2 = upper confidence limit) of recommended daily allowance (RDA), whereas those with IBW less than 120% reported 90, 67/120% (p less than 0.01). Patients with increased weights in comparison with IBW had higher hemoglobin A1c (HbA1c) levels (11.9 +/- 2.7%) than those with weights more appropriate for IBW (9.7 +/- 2.4%, p less than 0.025). IDDM patients reported overconsumption of protein and fat, but their carbohydrate intake was low. Analysis of dietary recalls revealed high protein intake (X +/- SD, 20.0 +/- 5.0% of total calorie intake), especially in older (27 +/- 4%) compared with younger (19 +/- 2%-19 +/- 4%, p less than 0.01) patients. Proportions of carbohydrate, protein, and fat did not correlate with variations in body weight and/or HbA1c. The reported intake of protein per kilogram body weight was not significantly different between appropriate-weight and overweight IDDM patients. There was no significant difference in reported total energy intakes of IDDM patients compared with their healthy control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)