Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 44
Filter
1.
Trials ; 23(1): 282, 2022 Apr 11.
Article in English | MEDLINE | ID: mdl-35410241

ABSTRACT

BACKGROUND: Diabetes self-management is a mainstay of diabetes care, but the implementation of self-management regimens into daily life is complex and often results in discouragement and distress. Modern approaches such as smartphone-based self-management applications are therefore needed to support people with diabetes. Since reimbursability would increase the availability of such digital applications to people with diabetes, we designed a study that meets all scientific and methodological requirements set by the German Digital Healthcare Act to allow reimbursement for a specific application (mySugr PRO). Here, we report the protocol of this study that aims at evaluating the efficacy of the digital self-management application with regard to patient-reported outcomes and medical benefits. METHODS/DESIGN: This multicenter, open-label, randomized, parallel-group, controlled trial will evaluate the health care effects and medical benefits of mySugr PRO. A total of 466 people with diabetes will be randomly allocated (2:1 randomization) to the interventional group (n = 311) that will use the digital self-management application during the 12-week study period or the control group (n = 155; no usage of the application). Baseline and follow-up examinations will assess diabetes distress as the primary endpoint as well as empowerment, HbA1c, blood glucose data, self-management, general well-being, and treatment satisfaction as secondary endpoints. Statistical analyses will use an intention-to-treat procedure (using multiple imputation for missing values) as well as a per-protocol approach for sensitivity analysis. DISCUSSION: To the best of our knowledge, this study will be one of the largest diabetes-specific evaluations of a digital health application supporting people with diabetes in their diabetes self-management that follow the requirements of the German Digital Healthcare Act. TRIAL REGISTRATION: German Clinical Trial Register DRKS00022923 . Registered on 22 October 2020.


Subject(s)
Diabetes Mellitus , Mobile Applications , Self-Management , Delivery of Health Care , Diabetes Mellitus/diagnosis , Diabetes Mellitus/therapy , Health Behavior , Humans , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Smartphone
2.
Diabet Med ; 37(3): 436-447, 2020 03.
Article in English | MEDLINE | ID: mdl-32017188

ABSTRACT

AIMS: To summarize the history, development and efficacy of diabetes self-management education on glycaemic control and mental health in adults and children or adolescents with type 1 diabetes and people with type 2 diabetes. A further aim was to review the status of implementation of diabetes self-management education into routine care and outline current gaps in implementation and research. METHODS: We searched PubMed and Google scholar for German- and English-language articles regarding diabetes self-management education, glycaemic control and mental health, and restricted this search to meta-analyses. RESULTS: Diabetes education has evolved from a compliance- and knowledge-oriented approach to an empowerment- and self-management-oriented approach. Diabetes self-management education seems to have a greater impact on glycaemic outcomes than on mental health outcomes, but the latter are rarely assessed. Technological development and digitalization can provide chances and challenges for diabetes self-management education. Digital solutions show promising results and great potential for improving the efficacy of diabetes self-management education further and providing ongoing support. The implementation of diabetes self-management education into routine clinical care frequently remains a challenge. CONCLUSION: Diabetes self-management education has been acknowledged as an essential part of diabetes therapy; however, current gaps regarding the efficacy of diabetes self-management education on mental health, and the need for education on the use of diabetes technology, are future avenues for research.


Subject(s)
Diabetes Mellitus , Patient Education as Topic/trends , Self-Management/trends , Diabetes Mellitus/epidemiology , Diabetes Mellitus/history , Diabetes Mellitus/psychology , Diabetes Mellitus/therapy , Health Behavior , History, 20th Century , History, 21st Century , Humans , Patient Education as Topic/history , Patient Education as Topic/methods , Self Care/history , Self Care/methods , Self Care/trends , Self-Management/history , Self-Management/methods
3.
Diabet Med ; 34(8): 1084-1091, 2017 08.
Article in English | MEDLINE | ID: mdl-28257159

ABSTRACT

AIMS: A self-management oriented education programme (MEDIAS 2 BSC) for people with Type 2 diabetes who are on a non-intensive insulin treatment regimen was developed. In a randomized, multi-centre trial, the effect of MEDIAS 2 BSC was compared with an established education programme that acted as a control group. METHODS: The primary outcome was the impact of MEDIAS 2 BSC on glycaemic control. Secondary outcomes included the incidence of severe hypoglycaemia, hypoglycaemia unawareness, diabetes-related distress, diabetes knowledge, quality of life and self-care behaviour. RESULTS: In total, 182 participants were randomized to the control group or MEDIAS 2 BSC [median age 64.0 (interquartile range 58.0-68.5) vs. 63.5 (57.0-70.0) years; HbA1c 62.8 ± 12.7 mmol/mol vs. 63.7 ± 14.0 mmol/mol; 7.9% ± 1.2% vs. 8.0% ± 1.3%]. After a 6-month follow-up, there was a mean decrease in HbA1c of 3.5 mmol/mol (0.32%) in the control group and 6.7 mmol/mol (0.61%) in MEDIAS 2 BSC. After adjusting for baseline differences and study centre, the mean difference between the groups was -3.3 mmol/mol [95% confidence interval (CI) -0.54 to -5.90 mmol/mol] [-0.30% (95% CI -0.05 to -0.54)] in favour of MEDIAS 2 BSC (P = 0.018). There were no increases in severe hypoglycaemia or hypoglycaemia unawareness. The education programmes had no significant effects on psychosocial outcome variables. CONCLUSION: MEDIAS 2 BSC was more effective in lowering HbA1c than the control condition. MEDIAS 2 BSC is a safe educational tool that improves glycaemic control without increasing the risk for hypoglycaemia. (Clinical Trials Registry No; NCT 02748239).


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hyperglycemia/prevention & control , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Patient Education as Topic , Self-Management/education , Aged , Combined Modality Therapy/adverse effects , Cost of Illness , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/therapy , Dose-Response Relationship, Drug , Follow-Up Studies , Germany/epidemiology , Glycated Hemoglobin/analysis , Health Knowledge, Attitudes, Practice , Humans , Hypoglycemia/chemically induced , Hypoglycemia/epidemiology , Hypoglycemia/physiopathology , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/adverse effects , Incidence , Insulin/administration & dosage , Insulin/adverse effects , Male , Middle Aged , Patient Compliance , Quality of Life , Risk Factors , Self Report , Severity of Illness Index
4.
Diabet Med ; 33(6): 835-43, 2016 06.
Article in English | MEDLINE | ID: mdl-26287511

ABSTRACT

AIMS: To compare the properties of the two most commonly used assessment tools for diabetes distress, the Problem Areas in Diabetes Scale (PAID) and the Diabetes Distress Scale (DDS), in order to discriminate their psychometric capabilities and functions. METHODS: Six hundred and twenty-eight people with diabetes (67% Type 1, 33% Type 2) were cross-sectionally assessed with the PAID, the DDS and further self-report scales regarding coping, quality of life, depressive symptoms and self-care, and medical data were gained. We analysed the PAID and DDS for areas of contentual/psychometric divergence in assessing diabetes distress and compared their associations with criteria of interest. RESULTS: Content analysis: The PAID covers a greater variety of emotional concerns and shows a stronger focus on food-related problems and complications. The DDS is more reflective of physician-related distress and problems concerning diabetes self-management. Psychometric analysis: Exploratory factor analyses revealed four-factor structures of both scales, explaining 60% (PAID) and 67% (DDS) of variance. Confirmatory factor analyses confirmed that single-factor and four-factor models fit the data. Total scales proved high and subscales mostly satisfactory reliability. Associations with criteria of interest: The PAID was significantly more strongly associated with dysfunctional coping styles, quality of life and depressive symptoms. The DDS showed significantly stronger associations with diabetes self-care and metabolic outcomes. CONCLUSION: Our results support both PAID and DDS as good self-report measures of diabetes distress. The observed contentual/psychometric differences suggest that a justified choice with regard to the intended clinical or scientific purpose can improve the acquisition of the required data.


Subject(s)
Diabetes Mellitus, Type 1/psychology , Diabetes Mellitus, Type 2/psychology , Stress, Psychological/diagnosis , Adaptation, Psychological , Adolescent , Adult , Aged , Depression/diagnosis , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 2/therapy , Humans , Middle Aged , Psychiatric Status Rating Scales , Psychometrics , Quality of Life , Self Care , Self Report , Surveys and Questionnaires , Young Adult
5.
Diabet Med ; 32(10): 1264-71, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26202341

ABSTRACT

AIM: To investigate the longitudinal bi-directionality of diabetes-related distress and depressive symptoms. METHODS: A total of 509 patients receiving intensified insulin therapy completed the Centre for Epidemiological Studies Depression scale questionnaire for the assessment of depressive symptoms as well as the Problem Areas in Diabetes questionnaire for the assessment of diabetes-related distress at baseline and at 6-month follow-up. Separate logistic and linear regression analyses for incidence and persistence were performed with demographic (age, gender, BMI) and medical (diabetes type, HbA1c , diabetes duration, late complications) control variables. RESULTS: Diabetes-related distress at baseline increased the risk of the incidence of elevated depressive symptoms by 2.56-fold (odds ratio 2.56; 95% CI 1.15-5.72; P = 0.02) when controlling for demographic and medical variables. In addition, diabetes-related distress at baseline doubled the chance of the persistence of elevated depressive symptoms (odds ratio 2.04, 95% CI 1.04-3.99; P = 0.04) when controlling for demographic and medical variables. The chance of having persistent elevated diabetes-related distress was increased 5.94-fold (odds ratio 5.94, 95% CI 2.60-13.59; P < 0.0001) when elevated depressive symptoms were present at baseline. None of the medical variables had an influence on incidence or persistence. CONCLUSIONS: Diabetes-related distress was identified as a risk factor for the incidence and persistence of depressive symptoms. Reducing diabetes-related distress could help to prevent the development of elevated depressive symptoms. Furthermore, depressive symptoms were identified as an amplifier for diabetes-related distress. Diabetes-related distress and depressive symptoms were independent risk factors for each other and should be monitored in routine care to disentangle their influence.


Subject(s)
Depression/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/psychology , Adult , Aged , Depression/complications , Diabetes Mellitus, Type 2/complications , Disease Progression , Female , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Psychiatric Status Rating Scales
7.
Diabetologia ; 45(4): 509-17, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12032626

ABSTRACT

AIMS/HYPOTHESIS: We hypothesized that beta-cell responses to changes in glucose would not be normal in subjects with impaired glucose tolerance (IGT). METHODS: Three groups of 6 subjects were studied: normal weight with normal glucose tolerance (control subjects); obese with normal glucose tolerance (Obese-NGT); and obese with IGT (Obese-IGT). All subjects had a graded glucose infusion protocol to increase (step-up) and then decrease (step-down) plasma glucose. We obtained average insulin-secretion rates (ISR) over the glucose range common to all three groups during step-up and step-down phases, minimal model indices of beta-cell function (f(b), f(d), f(s), T(up), T(down) ), and insulin sensitivity (Si). RESULTS: ISR differed significantly between step-up and -down phases only in Obese-IGT individuals. Basal (f(b)) and stimulated (f(d), f(s)) beta-cell sensitivity to glucose were similar in the three groups. Delays between glucose stimulus and beta-cell response during both step-up (T(up)) and -down (T(down)) phases were higher in Obese-IGT compared to Controls and Obese-NGT individuals. The product ISR x Si (10(-5.)min(-2) x l) was lower in Obese-IGT compared to Controls, both during step-up (919 +/- 851 vs 3192 +/- 1185, p < 0.05) and step-down (1455 +/- 1203 vs 3625 +/- 691, p < 0.05) phases. Consistently, the product f(s) x Si (10(-14.)min(-2). pmol(-1) x l) was lower in Obese-IGT than in control subjects (27.6 +/- 25.4 vs 103.1 +/- 20.2, p < 0.05). CONCLUSION/INTERPRETATION: Subjects with IGT are not able to secrete insulin to compensate adequately for insulin resistance. They also show delays in the timing of the beta-cell response to glucose when glucose levels are either rising or falling.


Subject(s)
Blood Glucose/metabolism , Diabetes Mellitus/physiopathology , Glucose Intolerance/physiopathology , Insulin/metabolism , Adult , Area Under Curve , C-Peptide/blood , Diabetes Mellitus/blood , Fasting , Female , Glucose Clamp Technique , Glucose Intolerance/blood , Glucose Tolerance Test , Homeostasis , Humans , Insulin/blood , Insulin Secretion , Male , Obesity/blood , Obesity/physiopathology
8.
J Clin Endocrinol Metab ; 86(5): 2027-31, 2001 May.
Article in English | MEDLINE | ID: mdl-11344202

ABSTRACT

Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders of reproductive age women, is associated with an increased risk of type 2 diabetes mellitus. Defects in both insulin action and insulin secretion contribute to this predisposition to diabetes, but the extent to which these defects are heritable among PCOS families has not been examined. In the present study we used the frequently sampled iv glucose tolerance test to quantitate insulin secretion (AIRg), insulin action (Si), and their product (AIRg x Si) among women with PCOS (n = 33) and their nondiabetic first degree relatives (n = 48). We then quantitated the heritability of these measures from familial correlations estimated within a genetic model. Familial (spousal, rhoMF; parent-offspring, rhoPO; and sibling, rhoSS) correlations were derived for log-transformed body mass index (BMI) as well as for AIRg, Si, and AIRg x Si, the latter three of which were adjusted for BMI. There was no evidence of significant heritability for either lnBMI or lnSi in these families. In contrast, the sibling correlation (rhoSS = 0.74) for lnAIRg was highly significant (chi(2) = 7.65; 1 df; P = 0.006). In addition, the parameter quantitating insulin secretion in relation to insulin sensitivity [i.e. ln(AIRg x Si)] was significant among siblings (rho(SS) = 0.74; chi(2) = 4.32; 1 df; P = 0.04). In summary, the results of the present study indicate that there is an heritable component to beta-cell dysfunction in families of women with PCOS. We conclude that heritability of beta-cell dysfunction is likely to be a significant factor in the predisposition to diabetes in PCOS.


Subject(s)
Insulin/metabolism , Polycystic Ovary Syndrome/genetics , Adolescent , Adult , Body Mass Index , Diabetes Mellitus, Type 2/etiology , Female , Humans , Insulin/pharmacology , Insulin Secretion , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/metabolism
9.
J Clin Endocrinol Metab ; 86(4): 1626-32, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11297595

ABSTRACT

We hypothesized that the administration of troglitazone, an insulin-sensitizing agent of the thiazolidinedione class, would improve the ovulatory dysfunction, hirsutism, hyperandrogenemia, and hyperinsulinemia of polycystic ovary syndrome (PCOS) patients. Four hundred and ten premenopausal women with PCOS in a multicenter, double blind trial were randomly assigned to 44 weeks of treatment with placebo (PBO) or troglitazone [150 mg/day (TGZ-150), 300 mg/day (TGZ-300), or 600 mg/day (TGZ-600)]. We compared changes in ovulatory function (by monitoring the urinary level of pregnanediol-3-glucuronide daily), hirsutism (by a modified Ferriman-Gallwey scoring method), hormonal levels (total and free testosterone, androstenedione, sex hormone-binding globulin, LH, FSH, and the LH/FSH ratio), and measures of glycemic parameters (fasting levels of glucose, insulin, hemoglobin A(1c), and the glucose and insulin areas under the curve during an oral glucose challenge) among study groups. Of the 410 patients recruited, 305 (74.4%) met evaluability criteria and were included in the analyses. The patients' baseline characteristics were similar across all treatment arms. Ovulatory rates were significantly greater for patients receiving TGZ-300 and TGZ-600 than for those receiving PBO (0.42 and 0.58 vs. 0.32; P < 0.05 and 0.0001, respectively). Of PCOS patients treated with TGZ-600, 57% ovulated over 50% of the time compared with 12% of placebo-treated patients. There was a significant decrease in the Ferriman-Gallwey score with TGZ-600 compared with PBO (0.22 +/- 0.53 vs. -2.21 +/- 0.49; P < 0.05, respectively). Free testosterone decreased and sex hormone-binding globulin increased in a dose-related fashion with troglitazone treatment, and all three troglitazone treatment groups were significantly different from placebo. Nearly all glycemic parameters showed dose-related decreases with troglitazone treatment. The total number and severity of adverse events (including elevations in liver enzymes) and the proportion of patients withdrawn from the study due to the development of adverse effects were similar between treatment groups. Troglitazone improves the ovulatory dysfunction, hirsutism, hyperandrogenemia, and insulin resistance of PCOS in a dose-related fashion, with a minimum of adverse effects.


Subject(s)
Chromans/therapeutic use , Hirsutism/drug therapy , Hirsutism/etiology , Ovulation/drug effects , Polycystic Ovary Syndrome/drug therapy , Polycystic Ovary Syndrome/physiopathology , Thiazoles/therapeutic use , Thiazolidinediones , Adult , Androgens/blood , Blood Glucose/analysis , Chromans/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Gonadotropins/blood , Humans , Polycystic Ovary Syndrome/complications , Pregnancy , Thiazoles/adverse effects , Troglitazone
10.
Am J Physiol Endocrinol Metab ; 280(1): E2-10, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11120653

ABSTRACT

Availability of quantitative indexes of insulin secretion is important for definition of the alterations in beta-cell responsivity to glucose associated with different physiopathological states. This is presently possible by using the intravenous glucose tolerance test (IVGTT) in conjunction with the C-peptide minimal model. However, the secretory response to a more physiological slowly increasing/decreasing glucose stimulus may uncover novel features of beta-cell function. Therefore, plasma C-peptide and glucose data from a graded glucose infusion protocol (seven 40-min periods of 0, 4, 8, 16, 8, 4, and 0 mg. kg(-1). min(-1)) in eight normal subjects were analyzed by use of a new model of insulin secretion and kinetics. The model assumes a two-compartment description of C-peptide kinetics and describes the stimulatory effect on insulin secretion of both glucose concentration and the rate at which glucose increases. It provides in each individual the insulin secretion profile and three indexes of pancreatic sensitivity to glucose: Phi(s), Phi(d), and Phi(b), related, respectively, to the control of insulin secretion by the glucose level (static control), the rate at which glucose increases (dynamic control), and basal glucose. Indexes (means +/- SE) were Phi(s) = 18.8 +/- 1.8 (10(9) min(-1)), Phi(d) = 222 +/- 30 (10(9)), and Phi(b) = 5.2 +/- 0.4 (10(9) min(-1)). The model also allows one to quantify the beta-cell times of response to increasing and decreasing glucose stimulus, equal to 5.7 +/- 2.2 (min) and 17.8 +/- 2.0 (min), respectively. In conclusion, the graded glucose infusion protocol, interpreted with a minimal model of C-peptide secretion and kinetics, provides a quantitative assessment of pancreatic function in an individual. Its application to various physiopathological states should provide novel insights into the role of insulin secretion in the development of glucose intolerance.


Subject(s)
B-Lymphocytes/immunology , Blood Glucose/metabolism , C-Peptide/blood , Insulin/metabolism , Models, Biological , Adult , B-Lymphocytes/metabolism , Female , Glucose Tolerance Test , Humans , Insulin Secretion , Male
11.
J Pediatr Endocrinol Metab ; 13 Suppl 5: 1285-9, 2000.
Article in English | MEDLINE | ID: mdl-11117671

ABSTRACT

We performed gonadotropin releasing hormone agonist (GnRHag) tests on 23 consecutive hyperandrogenic girls 9.9-17.5 years of age who were referred to our pediatric endocrinology clinic with symptoms suggestive of PCOS. They were compared to contemporaneously studied groups of adult normal and hyperandrogenic women. We found that hyperandrogenic adolescents had clinical and endocrine features similar to those of hyperandrogenic adults. However, there were some noteworthy unique features of adolescent hyperandrogenism, such as presentation in mid-childhood with premature pubarche and the occasional diagnosis before the age of 10 years. Some differences between adolescents and adults were statistically significant, for example, pelvic ultrasonography was not as helpful in the diagnosis of FOH as it is in adults. Nevertheless, a number of questions about the development of the ovarian dysfunction remain to be answered. For example, we are unable to diagnose ovarian dysfunction before puberty or in early puberty, and the relationship of "physiologic adolescent anovulation" to PCOS remains to be defined.


Subject(s)
Polycystic Ovary Syndrome/diagnosis , Adolescent , Adrenocorticotropic Hormone , Child , Dexamethasone , Female , Glucocorticoids , Gonadotropin-Releasing Hormone/agonists , Humans , Ovarian Function Tests , Polycystic Ovary Syndrome/complications , Puberty, Precocious/complications , Ultrasonography
12.
J Pediatr Endocrinol Metab ; 13 Suppl 5: 1299-301, 2000.
Article in English | MEDLINE | ID: mdl-11117674

ABSTRACT

Women with polycystic ovary syndrome (PCOS) are at increased risk of developing diabetes mellitus type 2. Insulin resistance plays a key role in the predisposition to diabetes in PCOS; however, defects in insulin secretion also appear to contribute to its development. Since diabetes mellitus is not a universal consequence in PCOS, however, it is important to develop means to identify those women who are at highest risk. In this way, it may become possible to delay or even prevent the onset of diabetes mellitus in later life. Identification of genetic factors and use of pharmacological agents may allow early identification of those women with PCOS who are at greatest risk for development of diabetes mellitus type 2.


Subject(s)
Glucose Intolerance/etiology , Islets of Langerhans/physiopathology , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/physiopathology , Dexamethasone/therapeutic use , Female , Glucocorticoids/therapeutic use , Humans , Insulin Resistance , Polycystic Ovary Syndrome/drug therapy
14.
Fertil Steril ; 72(2): 360-3, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10439012

ABSTRACT

OBJECTIVE: To determine whether a mutation in the GnRH receptor gene is responsible for polycystic ovary syndrome (PCOS). DESIGN: Molecular analysis of human genomic DNA. SETTING: Academic research environment. PATIENT(S): Eighty patients with PCOS. INTERVENTION(S): Extraction and polymerase chain reaction (PCR) analysis of genomic DNA, confirmation of PCR products by ethidium bromide staining of agarose gels after electrophoresis, denaturing gradient gel electrophoresis of PCR products, and photography. MAIN OUTCOME MEASURE(S): Mutations in the GnRH receptor of women with PCOS. RESULT(S): Denaturing gradient gel electrophoresis revealed no mutations in the exonic sequence encoding the open reading frame of the GnRH receptor. CONCLUSION(S): A mutation in the GnRH receptor gene is unlikely to be the underlying cause of PCOS in most patients. The molecular basis of this disorder remains unknown.


Subject(s)
DNA Mutational Analysis , Polycystic Ovary Syndrome/genetics , Receptors, LHRH/genetics , Adolescent , Adult , Exons , Female , Humans , Open Reading Frames , Polymerase Chain Reaction/methods
16.
Proc Natl Acad Sci U S A ; 96(15): 8573-8, 1999 Jul 20.
Article in English | MEDLINE | ID: mdl-10411917

ABSTRACT

Polycystic ovary syndrome (PCOS) is a common endocrine disorder of women, characterized by hyperandrogenism and chronic anovulation. It is a leading cause of female infertility and is associated with polycystic ovaries, hirsutism, obesity, and insulin resistance. We tested a carefully chosen collection of 37 candidate genes for linkage and association with PCOS or hyperandrogenemia in data from 150 families. The strongest evidence for linkage was with the follistatin gene, for which affected sisters showed increased identity by descent (72%; chi(2) = 12.97; nominal P = 3.2 x 10(-4)). After correction for multiple testing (33 tests), the follistatin findings were still highly significant (P(c) = 0.01). Although the linkage results for CYP11A were also nominally significant (P = 0.02), they were no longer significant after correction. In 11 candidate gene regions, at least one allele showed nominally significant evidence for population association with PCOS in the transmission/disequilibrium test (chi(2) >/= 3.84; nominal P < 0.05). The strongest effect in the transmission/disequilibrium test was observed in the INSR region (D19S884; allele 5; chi(2) = 8.53) but was not significant after correction. Our study shows how a systematic screen of candidate genes can provide strong evidence for genetic linkage in complex diseases and can identify those genes that should have high (or low) priority for further study.


Subject(s)
Genetic Linkage , Glycoproteins/genetics , Polycystic Ovary Syndrome/genetics , Chromosome Mapping , Cytochrome P-450 Enzyme System/genetics , Female , Follistatin , Genetic Markers , Genotype , Humans , Hyperandrogenism/genetics , Nuclear Family , Oligomenorrhea/genetics , Phenotype
17.
Endocrinol Metab Clin North Am ; 28(2): 423-38, viii, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10352927

ABSTRACT

This article summarizes the relationship between insulin and androgen excess, with a focus on what is known regarding two related issues in polycystic ovary syndrome: (1) defects in insulin secretion in PCOS and their role in the development of glucose intolerance in this population; and (2) pharmacologic interventions designed to attenuate hyperinsulinemia and its sequelae in PCOS.


Subject(s)
Hyperinsulinism/drug therapy , Polycystic Ovary Syndrome/drug therapy , Female , Glucose Intolerance/etiology , Humans , Hyperinsulinism/etiology , Hypoglycemic Agents/therapeutic use , Insulin/metabolism , Insulin Secretion , Metformin/therapeutic use , Polycystic Ovary Syndrome/complications , Polycystic Ovary Syndrome/physiopathology
18.
Diabetes Care ; 22(1): 141-6, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10333916

ABSTRACT

OBJECTIVE: NIDDM occurs commonly among women with polycystic ovary syndrome (PCOS). The prevalence and natural history of its precursor, impaired glucose tolerance (IGT), is less well known. The objective of this study was to characterize the prevalence and incidence of glucose intolerance in a large cohort of women with well-characterized PCOS. RESEARCH DESIGN AND METHODS: A total of 122 women with clinical and hormonal evidence of PCOS were recruited from the Medicine, Endocrinology, Gynecology, and Pediatrics Clinics at the University of Chicago. All women had a standard oral glucose tolerance test (OGTT) with measurement of glucose and insulin levels. A subset of 25 women were subsequently restudied with the aim of characterizing the natural history of glucose tolerance in PCOS. RESULTS: Glucose tolerance was abnormal in 55 (45%) of the 122 women: 43 (35%) had IGT and 12 (10%) had NIDDM at the time of initial study. The women with NIDDM differed from those with normal glucose tolerance in that they had a 2.6-fold higher prevalence of first-degree relatives with NIDDM (83 vs. 31%, P < 0.01 by chi 2) and were significantly more obese (BMI 41.0 +/- 2.4 vs. 33.4 +/- 1.1 kg/m2, P < 0.01). For the entire cohort of 122 women, there was a significant correlation between fasting and 2-h glucose concentrations (r = 0.76, P < 0.0001); among the subset with IGT, the fasting glucose concentration was poorly predictive of the 2-h level (r = 0.25, NS). After a mean follow-up of 2.4 +/- 0.3 years (range 0.5-6.3), 25 women had a second OGTT. The glucose concentration at 2 h during the second glucose tolerance test was significantly higher than the 2-h concentration during the first study (161 +/- 9 vs. 139 +/- 6 mg/dl, P < 0.02). CONCLUSIONS: The prevalence of IGT and NIDDM in women with PCOS is substantially higher than expected when compared with age- and weight-matched populations of women without PCOS. The conversion from IGT to NIDDM is accelerated in PCOS. The fasting glucose concentration does not reliably predict the glucose concentration at 2 h after an oral glucose challenge, particularly among those with IGT, the subgroup at highest risk for subsequent development of NIDDM. We conclude that women with PCOS should periodically have an OGTT and must be closely monitored for deterioration in glucose tolerance.


Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Glucose Intolerance/epidemiology , Polycystic Ovary Syndrome/complications , Adult , Analysis of Variance , Blood Glucose/metabolism , Chicago/epidemiology , Diabetes Mellitus, Type 2/blood , Female , Follow-Up Studies , Glucose Intolerance/blood , Glucose Tolerance Test , Humans , Insulin/blood , Polycystic Ovary Syndrome/blood , Prevalence , Regression Analysis , Testosterone/blood
20.
J Clin Invest ; 100(3): 530-7, 1997 Aug 01.
Article in English | MEDLINE | ID: mdl-9239399

ABSTRACT

Impaired glucose tolerance (IGT) is associated with defects in both insulin secretion and action and carries a high risk for conversion to non-insulin-dependent diabetes mellitus (NIDDM). Troglitazone, an insulin sensitizing agent, reduces glucose concentrations in subjects with NIDDM and IGT but is not known to affect insulin secretion. We sought to determine the role of beta cell function in mediating improved glucose tolerance. Obese subjects with IGT received 12 wk of either 400 mg daily of troglitazone (n = 14) or placebo (n = 7) in a randomized, double-blind design. Study measures at baseline and after treatment were glucose and insulin responses to a 75-g oral glucose tolerance test, insulin sensitivity index (SI) assessed by a frequently sampled intravenous glucose tolerance test, insulin secretion rates during a graded glucose infusion, and beta cell glucose-sensing ability during an oscillatory glucose infusion. Troglitazone reduced integrated glucose and insulin responses to oral glucose by 10% (P = 0.03) and 39% (P = 0.003), respectively. SI increased from 1.3+/-0.3 to 2.6+/-0.4 x 10(-)5min-1pM-1 (P = 0.005). Average insulin secretion rates adjusted for SI over the glucose interval 5-11 mmol/liter were increased by 52% (P = 0.02), and the ability of the beta cell to entrain to an exogenous oscillatory glucose infusion, as evaluated by analysis of spectral power, was improved by 49% (P = 0.04). No significant changes in these parameters were demonstrated in the placebo group. In addition to increasing insulin sensitivity, we demonstrate that troglitazone improves the reduced beta cell response to glucose characteristic of subjects with IGT. This appears to be an important factor in the observed improvement in glucose tolerance.


Subject(s)
Chromans/administration & dosage , Glucose Intolerance/drug therapy , Glucose/administration & dosage , Hypoglycemic Agents/administration & dosage , Islets of Langerhans/metabolism , Thiazoles/administration & dosage , Thiazolidinediones , Administration, Oral , Adult , Animals , Double-Blind Method , Female , Glucose Intolerance/metabolism , Glucose Tolerance Test , Guinea Pigs , Humans , Male , Middle Aged , Treatment Outcome , Troglitazone
SELECTION OF CITATIONS
SEARCH DETAIL
...