Gestational Diabetes Mellitus
01 Mar 2005-Journal of Clinical Investigation (American Society for Clinical Investigation)-Vol. 115, Iss: 3, pp 485-491
TL;DR: Gestational diabetes mellitus (GDM) is defined as glucose intolerance of various degrees that is first detected during pregnancy and provides a unique opportunity to study the early pathogenesis of diabetes and to develop interventions to prevent the disease.
Abstract: Gestational diabetes mellitus (GDM) is defined as glucose intolerance of various degrees that is first detected during pregnancy. GDM is detected through the screening of pregnant women for clinical risk factors and, among at-risk women, testing for abnormal glucose tolerance that is usually, but not invariably, mild and asymptomatic. GDM appears to result from the same broad spectrum of physiological and genetic abnormalities that characterize diabetes outside of pregnancy. Indeed, women with GDM are at high risk for having or developing diabetes when they are not pregnant. Thus, GDM provides a unique opportunity to study the early pathogenesis of diabetes and to develop interventions to prevent the disease.
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TL;DR: Physical inactivity is a primary cause of most chronic diseases as discussed by the authors, and the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life.
Abstract: Chronic diseases are major killers in the modern era. Physical inactivity is a primary cause of most chronic diseases. The initial third of the article considers: activity and prevention definitions; historical evidence showing physical inactivity is detrimental to health and normal organ functional capacities; cause vs. treatment; physical activity and inactivity mechanisms differ; gene-environment interaction [including aerobic training adaptations, personalized medicine, and co-twin physical activity]; and specificity of adaptations to type of training. Next, physical activity/exercise is examined as primary prevention against 35 chronic conditions [Accelerated biological aging/premature death, low cardiorespiratory fitness (VO2max), sarcopenia, metabolic syndrome, obesity, insulin resistance, prediabetes, type 2 diabetes, non-alcoholic fatty liver disease, coronary heart disease, peripheral artery disease, hypertension, stroke, congestive heart failure, endothelial dysfunction, arterial dyslipidemia, hemostasis, deep vein thrombosis, cognitive dysfunction, depression and anxiety, osteoporosis, osteoarthritis, balance, bone fracture/falls, rheumatoid arthritis, colon cancer, breast cancer, endometrial cancer, gestational diabetes, preeclampsia, polycystic ovary syndrome, erectile dysfunction, pain, diverticulitis, constipation, and gallbladder diseases]. The article ends with consideration of deterioration of risk factors in longer-term sedentary groups; clinical consequences of inactive childhood/adolescence; and public policy. In summary, the body rapidly maladapts to insufficient physical activity, and if continued, results in substantial decreases in both total and quality years of life. Taken together, conclusive evidence exists that physical inactivity is one important cause of most chronic diseases. In addition, physical activity primarily prevents, or delays, chronic diseases, implying that chronic disease need not be an inevitable outcome during life.
1,753 citations
TL;DR: The trend toward older maternal age, the epidemic of obesity and diabetes, and the decrease in physical activity and the adoption of modern lifestyles in developing countries may all contribute to a true increase in the prevalence of gestational diabetes mellitus.
Abstract: Recent data show that gestational diabetes mellitus (GDM) prevalence has increased by ∼10–100% in several race/ethnicity groups during the past 20 years. A true increase in the prevalence of GDM, aside from its adverse consequences for infants in the newborn period, might also reflect or contribute to the current patterns of increasing diabetes and obesity, especially in the offspring. Therefore, the public health aspects of increasing GDM need more attention.
The frequency of GDM usually reflects the frequency of type 2 diabetes in the underlying population (1,2). Established risk factors for GDM are advanced maternal age, obesity, and family history of diabetes (3). Unquestionably, there are ethnic differences in the prevalence of GDM (4–15). In the U.S., Native Americans, Asians, Hispanics, and African-American women are at higher risk for GDM than non-Hispanic white women (4–6,8–11,13–15). In Australia, GDM prevalence was found to be higher in women whose country of birth was China or India than in women whose country of birth was in Europe or Northern Africa (7). GDM prevalence was also higher in Aboriginal women than in non-Aboriginal women (12). In Europe, GDM has been found to be more common among Asian women than among European women (16). The proportion of pregnancies complicated by GDM in Asian countries has been reported to be lower than the proportion observed in Asian women living in other continents (17). In India, GDM has been found to be more common in women living in urban areas than in women living in rural areas (18).
The trend toward older maternal age (19), the epidemic of obesity (20) and diabetes (21), and the decrease in physical activity (22) and the adoption of modern lifestyles in developing countries (23) may all …
1,045 citations
TL;DR: In this paper, a meta-analysis was conducted to better estimate the risk of gestational diabetes mellitus (GDM) among women who are overweight or obese compared with lean or normal-weight women.
Abstract: OBJECTIVE —Numerous studies in the U.S. and elsewhere have reported an increased risk of gestational diabetes mellitus (GDM) among women who are overweight or obese compared with lean or normal-weight women. Despite the number and overall consistency of studies reporting a higher risk of GDM with increasing weight or BMI, the magnitude of the association remains uncertain. This meta-analysis was conducted to better estimate this risk and to explore differences across studies.
RESEARCH DESIGN AND METHODS —We identified studies from three sources: 1 ) a PubMed search of relevant articles published between January 1980 and January 2006, 2 ) reference lists of publications selected from the PubMed search, and 3 ) reference lists of review articles on obesity and maternal outcomes published between January 2000 and January 2006. We used a Bayesian model to perform the meta-analysis and meta-regression. We included cohort-designed studies that reported obesity measures reflecting pregnancy body mass, that had a normal-weight comparison group, and that presented data allowing a quantitative measurement of risk.
RESULTS —Twenty studies were included in the meta-analysis. The unadjusted ORs of developing GDM were 2.14 (95% CI 1.82–2.53), 3.56 (3.05–4.21), and 8.56 (5.07–16.04) among overweight, obese, and severely obese compared with normal-weight pregnant women, respectively. The meta-regression analysis found no evidence that these estimates were affected by selected study characteristics (publication date, study location, parity, type of data collection [retrospective vs. prospective], and prevalence of GDM among normal-weight women).
CONCLUSIONS —Our findings indicate that high maternal weight is associated with a substantially higher risk of GDM.
828 citations
TL;DR: This work comprehensively reviewed available data in the past decade in an attempt to estimate the contemporary global prevalence of gestational diabetes mellitus by country and region and the risk of progression from GDM to T2DM.
Abstract: Despite the increasing epidemic of diabetes mellitus affecting populations at different life stages, the global burden of gestational diabetes mellitus (GDM) is not well assessed. Systematically synthesized data on global prevalence estimates of GDM are lacking, particularly among developing countries. The hyperglycemic intrauterine environment as exemplified in pregnancies complicated by GDM might not only reflect but also fuel the epidemic of type 2 diabetes mellitus (T2DM). We comprehensively reviewed available data in the past decade in an attempt to estimate the contemporary global prevalence of GDM by country and region. We reviewed the risk of progression from GDM to T2DM as well. Synthesized data demonstrate wide variations in both prevalence estimates of GDM and the risk of progression from GDM to T2DM. Direct comparisons of GDM burden across countries or regions are challenging given the great heterogeneity in screening approaches, diagnostic criteria, and underlying population characteristics. In this regard, collaborative efforts to estimate global GDM prevalence would be a large but important leap forward. Such efforts may have substantial public health implications in terms of informing health policy makers and healthcare providers for disease burden and for developing more targeted and effective diabetes prevention and management strategies globally.
800 citations
TL;DR: What is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration are discussed, are discussed.
Abstract: Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist—including insulin and lifestyle interventions—there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.
736 citations
Cites background from "Gestational Diabetes Mellitus"
...While there is evidence that GDM can occur in all three settings [20,21], the vast majority (~80%) of GDM cases present as β-cell dysfunction on a background of chronic insulin resistance, to which the normal insulin resistance of pregnancy is partially additive [22]....
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TL;DR: In this paper, the authors compared a lifestyle intervention with metformin to prevent or delay the development of Type 2 diabetes in nondiabetic individuals. And they found that the lifestyle intervention was significantly more effective than the medication.
Abstract: Background Type 2 diabetes affects approximately 8 percent of adults in the United States. Some risk factors — elevated plasma glucose concentrations in the fasting state and after an oral glucose load, overweight, and a sedentary lifestyle — are potentially reversible. We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes. Methods We randomly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo, metformin (850 mg twice daily), or a lifestyle modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week. The mean age of the participants was 51 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 34.0; 68 percent were women, and 45 percent were members of minority groups. Results The average follow-up was 2.8 years. The incidence of diabetes was 11.0, 7.8, and 4.8 cases per 100 person-years in the placebo, metformin, and lifestyle groups, respectively. The lifestyle intervention reduced the incidence by 58 percent (95 percent confidence interval, 48 to 66 percent) and metformin by 31 percent (95 percent confidence interval, 17 to 43 percent), as compared with placebo; the lifestyle intervention was significantly more effective than metformin. To prevent one case of diabetes during a period of three years, 6.9 persons would have to participate in the lifestyle-intervention program, and 13.9 would have to receive metformin. Conclusions Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk. The lifestyle intervention was more effective than metformin.
17,333 citations
TL;DR: It was deemed essential to develop an appropriate, uniform terminology and a functional, working classification of diabetes that reflects the current knowledge about the disease.
Abstract: the growth of knowledge regarding the etiology and pathogenesis of diabetes has led many individuals and groups in the diabetes community to express the need for a revision of the nomenclature, diagnostic criteria, and classification of diabetes. As a consequence, it was deemed essential to develop an appropriate, uniform terminology and a functional, working classification of diabetes that reflects the current knowledge about the disease. (1)
11,886 citations
TL;DR: Differences in rates of progression between ethnic groups was reduced by adjustment for various lengths of follow-up and testing rates, so that women appeared to progress to type 2 diabetes at similar rates after a diagnosis of GDM.
Abstract: OBJECTIVE —To examine factors associated with variation in the risk for type 2 diabetes in women with prior gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS —We conducted a systematic literature review of articles published between January 1965 and August 2001, in which subjects underwent testing for GDM and then testing for type 2 diabetes after delivery. We abstracted diagnostic criteria for GDM and type 2 diabetes, cumulative incidence of type 2 diabetes, and factors that predicted incidence of type 2 diabetes. RESULTS —A total of 28 studies were examined. After the index pregnancy, the cumulative incidence of diabetes ranged from 2.6% to over 70% in studies that examined women 6 weeks postpartum to 28 years postpartum. Differences in rates of progression between ethnic groups was reduced by adjustment for various lengths of follow-up and testing rates, so that women appeared to progress to type 2 diabetes at similar rates after a diagnosis of GDM. Cumulative incidence of type 2 diabetes increased markedly in the first 5 years after delivery and appeared to plateau after 10 years. An elevated fasting glucose level during pregnancy was the risk factor most commonly associated with future risk of type 2 diabetes. CONCLUSIONS —Conversion of GDM to type 2 diabetes varies with the length of follow-up and cohort retention. Adjustment for these differences reveals rapid increases in the cumulative incidence occurring in the first 5 years after delivery for different racial groups. Targeting women with elevated fasting glucose levels during pregnancy may prove to have the greatest effect for the effort required.
2,063 citations
TL;DR: Protection from diabetes in the troglitazone group was closely related to the degree of reduction in endogenous insulin requirements 3 months after randomization and persisted 8 months after study medications were stopped, and was associated with preservation of beta-cell compensation for insulin resistance.
Abstract: Type 2 diabetes frequently results from progressive failure of pancreatic beta-cell function in the presence of chronic insulin resistance. We tested whether chronic amelioration of insulin resistance would preserve pancreatic beta-cell function and delay or prevent the onset of type 2 diabetes in high-risk Hispanic women. Women with previous gestational diabetes were randomized to placebo (n = 133) or the insulin-sensitizing drug troglitazone (400 mg/day; n = 133) administered in double-blind fashion. Fasting plasma glucose was measured every 3 months, and oral glucose tolerance tests (OGTTs) were performed annually to detect diabetes. Intravenous glucose tolerance tests (IVGTTs) were performed at baseline and 3 months later to identify early metabolic changes associated with any protection from diabetes. Women who did not develop diabetes during the trial returned for OGTTs and IVGTTs 8 months after study medications were stopped. During a median follow-up of 30 months on blinded medication, average annual diabetes incidence rates in the 236 women who returned for at least one follow-up visit were 12.1 and 5.4% in women assigned to placebo and troglitazone, respectively (P < 0.01). Protection from diabetes in the troglitazone group 1) was closely related to the degree of reduction in endogenous insulin requirements 3 months after randomization, 2) persisted 8 months after study medications were stopped, and 3) was associated with preservation of beta-cell compensation for insulin resistance. Treatment with troglitazone delayed or prevented the onset of type 2 diabetes in high-risk Hispanic women. The protective effect was associated with the preservation of pancreatic beta-cell function and appeared to be mediated by a reduction in the secretory demands placed on beta-cells by chronic insulin resistance.
1,310 citations
"Gestational Diabetes Mellitus" refers background in this paper
...impaired glucose tolerance results in a reciprocal downregulation of insulin secretion (61), which in turn is associated with a reduction in the risk of diabetes and with preservation of β cell function (62)....
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...reductions in endogenous insulin requirements and ultimately associated with stabilization of pancreatic β cell function (62)....
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...That loss can be slowed or stopped through the treatment of insulin resistance in order to reduce of high insulin secretory demands (62)....
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TL;DR: Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous group of disorders characterized by nonketotic diabetes mellitus, an autosomal dominant mode of inheritance, an onset usually before the age of 25 years and frequently in childhood or adolescence, and a primary defect in the function of the beta cells of the pancreas.
Abstract: Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous group of disorders characterized by nonketotic diabetes mellitus, an autosomal dominant mode of inheritance, an onset usually before the age of 25 years and frequently in childhood or adolescence, and a primary defect in the function of the beta cells of the pancreas. MODY can result from mutations in any one of at least six different genes (Table 1). One of these genes encodes the glycolytic enzyme glucokinase (associated with MODY 2),3 and the other five encode transcription factors: hepatocyte nuclear factor (HNF) 4α (associated with MODY 1),4 HNF-1α (MODY . . .
1,068 citations
"Gestational Diabetes Mellitus" refers background in this paper
...These include mutations in genes coding for: (a) glucokinase (MODY 2) (29, 33–35); (b) hepatocyte nuclear factor 1α (MODY 3) (29); (c) and insulin promoter factor 1 (MODY 4) (29)....
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...Early-onset diabetes with a relevant family history (autosomal dominant inheritance for MODY; maternal inheritance for mitochondrial mutations) may provide a clue to the diagnosis....
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...Mutations that cause several subtypes of MODY have been found in women with GDM....
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...Some patients have mutations in autosomes (autosomal dominant inheritance pattern, commonly referred to as maturity-onset diabetes of the young [MODY], with genetic subtypes denoted as MODY 1, MODY 2, etc.)....
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...In addition, Ellard et al. (34) have provided 4 clinical criteria that have relatively high specificity for identifying women with the glucokinase mutations that cause 1 form of MODY, MODY2: (a) persisting fasting hyperglycemia (105–145 mg/dl) after pregnancy; (b) a small (less than 82 mg/dl) increment in glucose above the fasting level during a 75-g, 2-hour OGTT; (c) insulin treatment during at least 1 pregnancy but subsequently controlled on diet; and (d) a firstdegree relative with type 2 diabetes, GDM, or fasting serum or plasma glucose greater than 100 mg/dl....
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