Association between fear of hypoglycemia and physical activity in youth with type 1 diabetes: The SEARCH for diabetes in youth study.

BACKGROUND: Youth with type 1 diabetes (T1D) are encouraged to participate in physical activity (PA). Studies have identified fear of hypoglycemia (FOH) as a barrier to participating in PA. OBJECTIVES: To examine (a) PA patterns in youth with T1D by age group and (b) the relationship between both parental and youth FOH and youth PA. METHODS: A cross-sectional analysis from the SEARCH cohort study visit of youth ages 10 to 17 years with T1D (n = 1129) was conducted. Linear regression models estimated the association between self-reported number of days of vigorous PA (VPA) and moderate PA (MPA) and both youth- and parent-reported FOH. Multivariable models were adjusted for age, sex, race, duration of T1D, HbA1c, use of continuous glucose monitoring (CGM), recent severe hypoglycemia, primary insulin regimen, and BMI. RESULTS: Participants were 52% female, had mean (sd) age 14.4 (4.2) years, diabetes duration 7.5 years (1.8), HbA1c 9.2% (1.7). Older youth were less likely to engage in VPA (P < .01), or sports teams (P < .01), but more likely to engage in MPA (P < .01). Higher youth FOH (behavior subscale) was associated with increased levels of VPA (ß (se) 0.30 (0.11), P = .01) but not significantly associated with MPA (P = .06). There was no statistically significant association between parental FOH and youth PA. CONCLUSIONS: In SEARCH participants with T1D, VPA, and team sports participation declined with age, while MPA increased. We observed that higher scores on the youth FOH behavioral subscale were associated with increased VPA levels, suggesting that FOH may be less of a barrier to PA than previously thought.

Family involvement with the diabetes regimen in young people: the role of adolescent depressive symptoms.

AIMS: In young people with Type 1 diabetes, depressive symptoms and shared responsibility for management of diabetes impact upon diabetes management and control. However, the simultaneous effects of both depressive symptoms and parental involvement on diabetes self-care and glycaemic control have not been examined. Thus, the aim of the current study was to examine the relationships between parental involvement and adolescent depressive symptoms in predicting blood glucose monitoring and glycaemic control. METHODS: One hundred and fifty young people with Type 1 diabetes (mean age 15.3 years) and their parents completed responsibility sharing and depressive symptom assessments, meter assessment of blood glucose monitoring and HbA(1c) at baseline and then 6, 12 and 18 months. RESULTS: Parental involvement affected HbA1c through blood glucose monitoring only at low levels of adolescent depressive symptoms (score ≤ 6), which made up only 20% of the sample. In the presence of more depressive symptoms, parental involvement no longer was related to HbA1c through blood glucose monitoring. This was the relationship in the majority of the sample (80%). CONCLUSIONS: While most young people in this sample are not showing evidence of high levels of depressive symptoms, even modest levels of distress interfere with parental involvement in diabetes management. By addressing adolescent depressive symptoms, interventions promoting parental involvement in these families may be more effective.

Clinical evolution of beta cell function in youth with diabetes: the SEARCH for Diabetes in Youth study.

AIMS/HYPOTHESIS: Few studies have explored the epidemiology of beta cell loss in youth with diabetes. This report describes the evolution and major determinants of beta cell function, assessed by fasting C-peptide (FCP), in the SEARCH for Diabetes in Youth study. METHODS: Participants were 1,277 youth with diabetes (948 positive for diabetes autoantibodies [DAs] and 329 negative for DAs), diagnosed when aged <20 years, who were followed from a median of 8 months post diagnosis, for approximately 30 months. We modelled the relationship between rate of change in log FCP and determinants of interest using repeated measures general linear models. RESULTS: Among DA-positive youth, there was a progressive decline in beta cell function of 4% per month, independent of demographics (age, sex, race/ethnicity), genetic susceptibility to autoimmunity (HLA risk), HbA(1c) and BMI z score, or presence of insulin resistance. Among DA-negative youth, there was marked heterogeneity in beta cell loss, reflecting an aetiologically mixed group. This group likely includes youths with undetected autoimmunity (whose decline is similar to that of DA-positive youth) and youth with non-autoimmune, insulin-resistant diabetes, with limited decline (~0.7% per month). CONCLUSIONS/INTERPRETATION: SEARCH provides unique estimates of beta cell function decline in a large sample of youth with diabetes, indicating that autoimmunity is the major contributor. These data contribute to a better understanding of clinical evolution of beta cell function in youth with diabetes, provide strong support for the aetiological classification of diabetes type and may inform tertiary prevention efforts targeted at high-risk groups.

Insulin resistance and arterial stiffness in healthy adolescents and young adults.

AIMS/HYPOTHESIS: Increased arterial stiffness is a risk factor for adverse cardiovascular events in adults with obesity-related insulin resistance (IR) or type 2 diabetes mellitus. Adolescents with type 2 diabetes have stiffer vessels. Whether stiffness is increased in obesity/IR in youth is not known. We sought to determine if IR was a determinant of arterial stiffness in youth, independent of obesity and cardiovascular risk factors. METHODS: We measured cardiovascular risk factors, IR, adipocytokines and arterial stiffness (brachial artery distensibility [BrachD], pulse wave velocity [PWV]) and wave reflection (augmentation index [AIx]) in 343 adolescents and young adults without type 2 diabetes (15-28 years old, 47% male, 48% non-white). Individuals <85th percentile of BMI were classified as lean (n = 232). Obese individuals were grouped by HOMA index as not insulin resistant (n = 46) or insulin resistant (n = 65) by the 90th percentile for HOMA for lean. Mean differences were evaluated by ANOVA. Multivariate models evaluated whether HOMA was an independent determinant of arterial stiffness. RESULTS: Risk factors deteriorated from lean to obese to obese/insulin resistant (all p ≤ 0.017). Higher AIx, lower BrachD and higher PWV indicated increased arterial stiffness in obese and obese/insulin-resistant participants. HOMA was not an independent determinant. Age, sex, BMI and BP were the most consistent determinants, with HDL-cholesterol playing a role for BrachD and leptin for PWV (AIx R²= 0.34; BrachD R² = 0.37; PWV R² = 0.40; all p ≤ 0.02). CONCLUSIONS/INTERPRETATION: Although IR is associated with increased arterial stiffness, traditional cardiovascular risk factors, especially obesity and BP, are the major determinants of arterial stiffness in healthy young people.

Association testing of TCF7L2 polymorphisms with type 2 diabetes in multi-ethnic youth.

AIM/HYPOTHESIS: Common variants in the transcription factor 7-like 2 (TCF7L2) gene have been associated with type 2 diabetes in adults. However, it is not known whether TCF7L2 variation increases the risk of early onset type 2 diabetes. Using a case-control design, we examined whether the reported variants [rs12255372 (T/G) and rs7903146 (T/C)] are associated with type 2 diabetes in SEARCH for Diabetes in Youth study participants. METHODS: Variants were genotyped in 694 non-Hispanic white (NHW) youth (86 cases, mean age 15.5 years, mean BMI 34.8; and 608 controls, mean age 14.4 years, mean BMI 22.3) and 545 African-American (AA) youth (154 cases, mean age 15.9, mean BMI 37; and 391 controls, mean age 14.8, mean BMI 23.8). Logistic regression adjusted for age, sex, BMI and West African ancestry. RESULTS: The association of the risk T allele with case/control status was different in AA and NHW youth (p = 0.025). Among AA youth, each copy of the T allele (rs7903146) was associated with a 1.97-fold (1.37, 2.82) increased odds for type 2 diabetes (p < 0.0001), after adjustment for age, sex, BMI and African ancestry. No significant association was detected in NHW youth (adjusted OR, 1.14; 0.73, 1.79). CONCLUSION/INTERPRETATION: TCF7L2 variation is associated with an increased risk of early-onset type 2 diabetes among AA youth, and the association appears to be stronger in AA than NHW youth. This suggests potential different contributions of genetic and environmental factors to early-onset type 2 diabetes by race.

The effects of obesity and type 2 diabetes mellitus on cardiac structure and function in adolescents and young adults.

AIMS/HYPOTHESIS: We sought to evaluate the effects of obesity and obesity-related type 2 diabetes mellitus on cardiac geometry (remodelling) and systolic and diastolic function in adolescents and young adults. METHODS: Cardiac structure and function were compared by echocardiography in participants who were lean, obese or obese with type 2 diabetes (obese diabetic), in a cross sectional study. Group differences were assessed using ANOVA. Independent determinants of cardiac outcome measures were evaluated with general linear models. RESULTS: Adolescents with obesity and obesity-related type 2 diabetes were found to have abnormal cardiac geometry compared with lean controls (16% and 20% vs <1%, p < 0.05). These two groups also had increased systolic function. Diastolic function decreased from the lean to obese to obese diabetic groups with the lowest diastolic function observed in the obese diabetic group (p < 0.05). Regression analysis showed that group, BMI z score (BMIz), group × BMIz interaction and systolic BP z score (BPz) were significant determinants of cardiac structure, while group, BMIz, systolic BPz, age and fasting glucose were significant determinants of the diastolic function (all p < 0.05). CONCLUSIONS/INTERPRETATION: Adolescents with obesity and obesity-related type 2 diabetes demonstrate changes in cardiac geometry consistent with cardiac remodelling. These two groups also demonstrate decreased diastolic function compared with lean controls, with the greatest decrease observed in those with type 2 diabetes. Adults with diastolic dysfunction are known to be at increased risk of progressing to heart failure. Therefore, our findings suggest that adolescents with obesity-related type 2 diabetes may be at increased risk of progressing to early heart failure compared with their obese and lean counterparts.

Gender differences in the relationships among obesity, adiponectin and brachial artery distensibility in adolescents and young adults.

BACKGROUND: Obesity-related cardiovascular diseases (CVDs) are a major cause of cardiovascular (CV) mortality. Obesity-related reduction in vascular protective adipose-derived proteins, such as adiponectin (APN), has an important role. METHODS: We compared brachial artery distensibility (BrachD) with APN, the level of adiposity and other CV risk factors (CVRFs) in 431 post-pubertal subjects (mean 17.9 years). Gender differences in average values were examined by t-tests. Correlations among BrachD, obesity and other CVRFs were examined. Regression analysis was performed to determine whether APN provided an independent contribution to BrachD, while controlling for obesity and other CVRFs. RESULTS: Male subjects had lower BrachD (5.72+/-1.37 vs 6.45+/-1.60% change per mm Hg, P<0.0001) and lower APN (10.50+/-4.65 vs 13.20+/-6.53; all P<0.04) than female subjects. BrachD correlated with APN (r=0.25, P< 0.0001). Both BrachD and APN correlated with measures of body size, including height, weight and body mass index (BMI). Both correlated with higher systolic blood pressure, glucose, insulin and lower high-density lipoprotein cholesterol (all P<0.01). In multivariate analysis, APN, gender, APN*gender and BMI z-score predicted BrachD (r(2)=0.305). On the basis of gender difference, only BMI z-score was significant for male subjects (r(2)=0.080), whereas APN and BMI z-score contributed for female subjects (r(2)=0.242, all P<0.0001). CONCLUSIONS: BrachD is independently influenced by obesity in both male and female subjects. In female subjects, APN exerts an additional independent effect even after adjusting for blood pressure (BP), lipid levels and insulin. Differences in the effect of the APN-adiposity relationship on obesity-related vascular disease may be one reason for gender differences in the development and progression of atherosclerosis.

Urinary symptoms and quality of life in women following urogenital fistula repair: a long-term follow-up study.

Using the Bristol Female Lower Urinary Tract Symptom questionnaire, we have investigated urinary and sexual symptoms and quality of life in a group of 31 women 50 months (median) after successful repair of urogenital fistula. All had undergone urodynamic investigation prior to their repair surgery, and only 36% had normal findings. Almost all women reported one or more symptoms, and for 65%, these caused at least 'a bit of a problem', although 87% said that their urinary symptoms had little or no impact on their quality of life. Symptoms were similar in urethrovaginal and vesicovaginal fistulae and were not significantly associated with prior functional abnormality.

Backache in gynaecologists.

The objectives of the study were to assess the overall prevalence of backache in gynaecologists and determine its impact on work, and to identify possible occupational risk factors. The sample comprised gynaecologists, both active and retired, listed as members of the Ulster Obstetrical and Gynaecological Society, who were asked to complete and return a postal questionnaire. The response rate was 94% (107/114). The prevalence of backache, which included pain arising in the thoracic and lumbosacral regions, was 72%. Fifty-three per cent of those with back pain blamed it on working in obstetrics and gynaecology. Overall, 32% of gynaecologists required a change of their work practice, 20% had taken time off work and 8% had required surgery. We conclude that significant morbidity results from backache in gynaecologists. This has economic implications and requires further assessment to improve prevention, with emphasis on individual training and ergonomic evaluation of work-related postures.

First-phase insulin release during the intravenous glucose tolerance test as a risk factor for type 1 diabetes.

OBJECTIVE: To determine the relationship between first-phase (1 minute + 3 minutes) insulin production during the intravenous glucose tolerance test (IV-GTT) and risk factors for developing type 1 diabetes. STUDY DESIGN: Relatives of persons with type 1 diabetes (n = 59,600) were screened for islet cell antibodies (ICAs). Subjects who had positive screening results underwent IV-GTT (> or =2 times), repeat ICA screening, insulin autoantibody (IAA) screening twice, and an oral glucose tolerance test. RESULTS: Of the 59,600 subjects in the study, 2199 (3.69%) had positive findings on initial ICA test. IV-GTTs were performed in 1622 subjects, with children <8 years having the lowest first-phase insulin release (FPIR) and subjects 8 to 20 years of age having the highest FPIR. The FPIR was lower for subjects with a confirmed positive ICA test result or a positive IAA test result, subjects with higher titers of ICA or IAA, and subjects who had an abnormal (impaired or diabetic) oral glucose tolerance test result. CONCLUSION: FPIR in the IV-GTT correlates strongly with risk factors for development of type 1 diabetes.

The levonorgestrel intra-uterine system: therapeutic application in family planning.

OBJECTIVE: To assess the non-contraceptive benefits of the levonorgestrel intra-uterine system 12 months following insertion in a family planning setting. DESIGN: Postal questionnaire survey. SETTING: Family planning clinics at the Ulster and Bangor Hospitals. SUBJECTS: Eighty-six consecutive subjects fitted with the levonorgestrel intra-uterine system. RESULTS: Response rate 87.3%. Outcome measured in terms of compliance, satisfaction and menstrual symptomatology. Reasons for insertion were as follows: 21.7% contraception only; 65.2% menorrhagia, 24.6% dysmenorrhoea and 1.4% premenstrual syndrome. Duration of menses was 8.25 days pre-insertion and 2.41 days at 12 months. Of the subjects, 59.4% experienced at least one hormonal side effect; 10.1% of systems were removed within 12 months. At 12 months 86.9% of women were satisfied and 9.8% of women planned to discontinue. CONCLUSION: The levonorgestrel intra-uterine system was acceptable to almost 80% of women after 12 months, with significant reduction in duration of menses. Family planning clinics are an ideal setting to implement the guidelines for the initial management of menorrhagia.

The type 2 family: a setting for development and treatment of adolescent type 2 diabetes mellitus.

OBJECTIVE: To identify physical, behavioral, and environmental features of adolescents (aged 11-17 years) with type 2 diabetes mellitus and their families to define the involvement of known risk factors and to define a profile of at-risk individuals. DESIGN AND METHODS: A total of 42 subjects from 11 families with an adolescent in whom type 2 diabetes was previously diagnosed participated. All subjects underwent anthropometric measurement and completed food frequency and eating disorder questionnaires, and were classified according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. In addition, laboratory tests to determine levels of hemoglobin A1c, fasting glucose, C peptide, insulin, and proinsulin were performed. RESULTS: Type 2 diabetes had been diagnosed in 5 of 11 mothers and 4 of 11 fathers before the study. Type 2 diabetes was diagnosed in 3 of the remaining 7 fathers during the study. In 3 families, both parents were affected with type 2 diabetes. As a group, participants were obese, with a body mass index higher than the 95th percentile for probands and fathers, and higher than the 85th percentile for mothers and siblings. The sum of skin fold measurements was above the 95th percentile for the probands, their siblings, and the parents. All groups had high fat intake and low fiber intake. None of the subjects participated in a structured or routine exercise program, and most reported no regular physical activity. Three of the probands met the criteria for binge-eating disorder, and 6 additional patients had notable characteristics of the disorder. Mothers affected with type 2 diabetes had markedly abnormal hemoglobin A1c levels, indicating poor control. There were no group differences in fasting concentrations of insulin, proinsulin, or C peptide. However, a third of the mothers with type 2 diabetes, and all but 1 of the siblings, had evidence of insulin resistance. CONCLUSIONS: Adolescents in whom type 2 diabetes has been diagnosed, as well as their first-degree family members, are obese. In addition, the incidence of diagnosed and undiagnosed type 2 diabetes or of insulin resistance in the families of adolescents with type 2 diabetes is striking. Probands and other family members have lifestyles characterized by high fat intake, minimal physical activity, and a high incidence of binge eating. These findings indicate that the families of adolescents with type 2 diabetes share many anthropometric and lifestyle risk factors. The design of treatment programs for adolescents with type 2 diabetes will need to address the lifestyle and health habits of the entire family.

Urinary incontinence in Northern Ireland: a prevalence study.

OBJECTIVE: To determine the prevalence of urinary incontinence in a Northern Ireland community drawn from four neighbouring geographical areas and to assess factors predisposing to the development of urinary incontinence. SUBJECTS AND METHODS: A three-page self-administered postal questionnaire was sent to 1050 women (age range 35-74 years), recruited randomly from a target population of 43 829 women. The main survey was preceded by a pilot survey. Respondents and those not responding were compared. RESULTS: The overall response rate was 65.6% (689/1050); there was no significant difference between respondents and those not responding. Two-hundred and thirty-one women (33.5%) reported incontinence 'sometimes' and 161 (23.4%) 'often'. Of those who had urinary incontinence, sanitary protection was required by 21.7% (85/392). This equates to 12.3% (85) of the total study population. Age (chi2=20.34; P<0.001) and parity (Mann-Whitney U-test, P< 0.001) were associated with urinary incontinence, with a higher proportion of women aged 45-54 years having urinary incontinence. The menopause and postnatal pelvic floor exercises were not associated with urinary incontinence. Overall 19.9% (78/392) of women with urinary incontinence had consulted their general practitioner. Of those who required sanitary protection, 40% (34/85) had consulted their doctor. CONCLUSION: Urinary incontinence is common; it is sufficiently severe to require sanitary protection in 12% of women aged 35-74 years in a Northern Ireland community.

Nocturnal blood pressure in young patients with insulin-dependent diabetes mellitus: correlation with cardiac function.

Lack of a decline in nocturnal blood pressure is associated with an adverse effect on end organs in adults with insulin-dependent diabetes mellitus (IDDM). The role of the decline in nocturnal blood pressure in young patients with IDDM is not known. We studied 25 white subjects with IDDM (age = 20.8 +/- 3.7 years, mean +/- SD), 8 of whom were female. The duration of IDDM in these subjects was 12.9 +/- 5.4 years (mean +/- SD). We determined the values for glycosylated hemoglobin (HgbA1), 24-hour ambulatory blood pressure, diastolic cardiac function (the ratio of peak E wave to peak A wave velocity (E/A) and indexed peak filling rate ¿PFR/SV¿ by Doppler echocardiography), and albumin excretion rate. The HgbA1 level was 10.9% +/- 1.9% (mean +/- SD; normal range = 4.5%-8.5%). The HgbA1 concentration was inversely correlated (p < 0.005) with the decline in systolic (r = 0.57) and diastolic (r = -0.55) nocturnal blood pressure. Diastolic cardiac dysfunction ¿E/A ratio [r = 0.42, p < 0.03) and PFR/SV (r = 0.52, p < 0.01)¿ correlated with a smaller decrease in nocturnal diastolic blood pressure. An inverse correlation between decline in nocturnal systolic blood pressure and log albumin excretion rate (r = -0.37, p = 0.07) approached statistical significance. We conclude that poor glycemic control adversely affects nocturnal blood pressure and that the latter may play an important role in cardiac and possibly renal dysfunction in early IDDM.

Diastolic dysfunction in young patients with insulin-dependent diabetes mellitus as determined by automated border detection.

Diastolic dysfunction is an early harbinger for systolic dysfunction in insulin-dependent diabetes mellitus (IDDM). To determine the role of automated border detection (ABD) in detecting diastolic abnormalities and whether IDDM control correlates with abnormalities, 21 young IDDM patients (22 +/- 4 years old) and 19 control subjects underwent echocardiography. ABD indices included the percent contribution to total left ventricular filling of the three phases of diastole (rapid filling, diastasis, and atrial contraction) and peak filling rate. Doppler indices included E/A ratio and peak filling rate. Rapid filling phase was lower in the IDDM patients compared with control subjects (73% +/- 5% versus 80% +/- 5%, p = 0.0006), and atrial contraction filling was higher (19% +/- 4% versus 14% +/- 3%, p = 0.0003). Doppler indexes showed similar changes. Glycosylated hemoglobin, insulin dosage, and duration of IDDM since puberty were associated with filling abnormalities. Young patients with IDDM have increased atrial contraction and reduced rapid filling phases detected by automatic border detection, and these diastolic abnormalities are related to the diabetic disease process.

Diabetic ketoacidosis among obese African-American adolescents with NIDDM.

OBJECTIVE: To determine whether ketosis at the time of presentation occurs among African-American adolescents with NIDDM. RESEARCH DESIGN AND METHODS: We reviewed the charts of all islet cell antibody (ICA) negative patients diagnosed with NIDDM at Children's Hospital Medical Center (CHMC) between 1982 and 1995. RESULTS: Between 1982 and 1985, 70 adolescents were diagnosed with NIDDM. Of these, ICA determinations were available and negative on 42 subjects (28 African-American, 12 white). Twelve of 28 (42%) African-American patients presented with ketonuria, and seven of 28 (25%) presented with DKA. In comparison, none of the 12 white adolescents with NIDDM had ketonuria at presentation or during their subsequent course. Mean follow-up time for patients with ketosis at presentation was 24 months. There was no difference between the age, BMI, or sex distribution of patients with and without ketosis. Previously diagnosed hypertension was present in 42% of patients presenting with ketosis, compared with 17% of the general NIDDM population at CHMC. CONCLUSIONS: We conclude that ketosis may occur among African-American adolescents with NIDDM, as has been previously reported among African-American adults with NIDDM. Therefore, ketosis in obese young African-American patients with new-onset diabetes does not necessarily imply the presence of IDDM and insulin dependence.

6-Hydroxymelatonin sulfate excretion in human puberty.

We investigated the relationship of urinary excretion rate of 6-hydroxymelatonin sulfate (SM), the main metabolite of melatonin, with pubertal development and determined the day to day variability of SM excretion. Healthy subjects 4-31 years old completed one or multiple timed overnight urine collections. SM excretion rate per body size was significantly higher in 99 prepubertal subjects (35.5 +/- 2.3 ng/h/kg and 0.97 +/- 0.06 microgram/hr/m2) than in 86 pubertal subjects (18.1 +/- 1.1 ng/hr/kg and 0.61 +/- 0.03 microgram/hr/m2) or in 29 adults (15.0 +/- 1.5 ng/hr/kg and 0.59 +/- 0.06 microgram/hr/m2); no significant difference was present in pubertal stages 2 to 5. Among the prepubertal children, SM excretion rate in mid childhood was significantly higher than in late childhood. The variability of SM and creatinine excretion examined in 52 children, adolescents and adults with three or four collections was defined as the mean of the 52 coefficients of variation for the multiple measures in each subject. The variability of total nocturnal SM (25.9 +/- 2.6%) was similar to that of total creatinine (21.7 +/- 2.3%) and neither was significantly correlated with the variability in start time or duration of urine collection. The results suggest that, relative to body size, melatonin secretion rate is higher in mid childhood, decreases during late childhood, and remains stable from pubertal stage 2 to adulthood. The decline in melatonin secretion rate occurs during the developmental phase of disinhibition of the gonadotropin releasing hormone pulse generator. Hence, we infer that melatonin may be a suppressive factor of puberty during childhood. The substantial individual variability observed for SM excretion calls for caution in using single urine collections in longitudinal studies or in studies of drug responses.

Increased incidence of non-insulin-dependent diabetes mellitus among adolescents.

OBJECTIVE: To determine whether a rise in the diagnosis of non-insulin- dependent diabetes mellitus (NIDDM) has accompanied the rise in obesity in the pediatric population, as it has among adults. STUDY DESIGN: Medical records of 1027 consecutive patients from birth to age 19 years with a diagnosis of diabetes from 1982 to 1995 at a regional, university-affiliated pediatric diabetes referral center were reviewed and classified according to criteria of the National Diabetes Data Group. RESULTS: The number of patients with a diagnosis of NIDDM rose from approximately 4% of new diagnoses of diabetes in patients from birth to age 19 years before 1992, to 16% in 1994. Among patients 10 to 19 years of age, NIDDM accounted for 33% of diagnoses of diabetes in 1994. The incidence of adolescent NIDDM in Greater Cincinnati increased tenfold, from 0.7/100,000 per year in 1982 to 7.2/100,000 per year in 1994. The mean (+/- SD) age and body mass index at presentation were 13.8 +/- 1.9 years and 37.7 +/- 9.6 kg/m2, respectively. The overall female/male ratio was 1.7:1, and female patients were seen 1 year earlier than male patients (p < 0.01). Male subjects had a higher body mass index than female subjects (p < 0.05). A first-degree relative with NIDDM was identified for 65% of patients. At presentation, 21% of the patients had had a diagnosis of at least one other condition associated with obesity. CONCLUSION: There is an increasing incidence of NIDDM among adolescents in Greater Cincinnati, accompanying the national rise in adolescent obesity. Obesity and strong family histories of NIDDM are important risk factors. Because NIDDM leads to long-term morbidity, the prevention of obesity as well as early identification of overt disease, is critical.

Absence of molecular defect in the type II 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) gene in premature pubarche children and hirsute female patients with moderately decreased adrenal 3 beta-HSD activity.

To date the molecular basis and hormonal criteria for inherited mild late-onset 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency congenital adrenal hyperplasia (CAH) have not been defined. We have thus investigated the presence or absence of mutation in the type II 3 beta-HSD gene encoding adrenal/gonadal 3 beta-HSD in each of five premature pubarche children and hirsute female patients manifesting moderately decreased adrenal 3 beta-HSD activity. ACTH-stimulated hormonal levels in all patients compared with mean levels in pubertal stage-matched normal subjects were between 2.5 and 6.5 SD for 17-hydroxypregnenolone levels, and between 2.5 and 7 SD for dehydroepiandrosterone levels in all except one patient. 17-Hydroxypregnenolone to cortisol ratios were between 2.5 and 4.3 SD, and dehydroepiandrosterone to androstenedione ratios were between 3 and 8.6 SD. The type II 3 beta-HSD gene regions of a putative promoter, exons I, II, III, and IV, and exon-intron boundaries in all subjects were amplified by polymerase chain reaction and then sequenced. All patients had normal sequences of the type II 3 beta-HSD gene in both alleles. Three female patients heterozygotic for severe 3 beta-HSD deficiency CAH with one allele mutation of the gene demonstrated normal ACTH-stimulated hormone profiles. These data indicate that moderately decreased adrenal 3 beta-HSD activity resulting in modestly increased delta 5 precursor steroid levels and delta 5 to delta 4 steroid ratios in premature pubarche and hirsute patients is not caused by a mutation in the type II 3 beta-HSD gene.(ABSTRACT TRUNCATED AT 250 WORDS)