Assiamira Ferrara

Increasing Prevalence of Gestational Diabetes Mellitus A public health perspective

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 …

Risk of Bladder Cancer Among Diabetic Patients Treated With Pioglitazone: Interim report of a longitudinal cohort study

OBJECTIVE Some preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study examining the association between pioglitazone therapy and the risk of bladder cancer in patients with diabetes. RESEARCH DESIGN AND METHODS This study includes 193,099 patients in the Kaiser Permanente Northern California diabetes registry who were ≥40 years of age between 1997 and 2002. Those with prior bladder cancer were excluded. Ever use of each diabetes medication (defined as two or more prescriptions within 6 months) was treated as a time-dependent variable. Cox regression–generated hazard ratios (HRs) compared pioglitazone use with nonpioglitazone use adjusted for age, sex, race/ethnicity, diabetes medications, A1C, heart failure, household income, renal function, other bladder conditions, and smoking. RESULTS The group treated with pioglitazone comprised 30,173 patients. There were 90 cases of bladder cancer among pioglitazone users and 791 cases of bladder cancer among nonpioglitazone users. Overall, ever use of pioglitazone was not associated with risk of bladder cancer (HR 1.2 [95% CI 0.9–1.5]), with similar results in men and women (test for interaction P = 0.8). However, in the a priori category of >24 months of therapy, there was an increased risk (1.4 [1.03–2.0]). Ninety-five percent of cancers diagnosed among pioglitazone users were detected at early stage. CONCLUSIONS In this cohort of patients with diabetes, short-term use of pioglitazone was not associated with an increased incidence of bladder cancer, but use for more than 2 years was weakly associated with increased risk.

Isolated postchallenge hyperglycemia and the risk of fatal cardiovascular disease in older women and men. The Rancho Bernardo Study.

OBJECTIVE To determine whether diabetes defined by isolated postchallenge hyperglycemia (IPH) (2-h postchallenge plasma glucose ≥ 11.1 mmol/l with fasting plasma glucose [FPG] < 7.0 mmol/l) increases the risk of fatal cardiovascular disease (CVD) in older women and men. RESEARCH DESIGN AND METHODS In a prospective study, we followed 769 men and 1,089 women, aged 50–89 years, who had no history of diabetes or myocardial infarction and demonstrated no fasting hyperglycemia (i.e., FPG < 7.0 mmol/l) when they underwent oral glucose tolerance testing at baseline in 1984–1987. RESULTS At baseline, 70% of 125 women and 48% of 133 men with previously undiagnosed diabetes had IPH. Over the next 7 years, women with IPH had a significantly increased risk of fatal CVD and heart disease compared with nondiabetic women. This increased risk was not observed in men with IPH. This association was independent of age, hypertension, central obesity, cigarette smoking, HDL cholesterol, and triglycerides (multiply adjusted hazard ratio and 95% CI: 2.6 and 1.4–4.7 for CVD; 2.9 and 1.3–6.4 for heart disease). CONCLUSIONS Diabetes defined by IPH alone is common in older adults and more than doubles the risk of fatal CVD and heart disease in older women. Because the prevalence of IPH increases with age, the use of fasting glucose alone for diabetes screening or diagnosis may fail to identify most older adults at high risk for CVD and should be reevaluated.

An increase in the incidence of gestational diabetes mellitus: Northern California, 1991-2000.

OBJECTIVE: Women with gestational diabetes mellitus (GDM) and their offspring are at increased risk of developing diabetes. Although increases in diabetes prevalence have been reported in the United States, it is unknown whether this trend is also occurring for GDM. We examined trends in the yearly cumulative incidence of GDM between the years 1991 and 2000. METHODS: A cohort study of 267,051 pregnancies screened for GDM that occurred among members of the Northern California Kaiser Permanente Medical Care Program, representing 86.8% of all eligible pregnancies, was undertaken. RESULTS: GDM was identified in 14,175 pregnancies according to the diagnostic plasma glucose thresholds of the American Diabetes Association (96.5%) or the World Health Organization (3.5%). An additional 2,743 pregnant women with GDM were identified by a hospital discharge diagnosis. The women screened in 2000 were slightly older (mean [standard deviation] age 28.8 [6.0] years) than were those screened in 1991 (28.2 [5.7] years) and more likely to be from minority ethnic groups (51.4% versus 37.3% identified as African American, Asian, Hispanic, and other). The age- and ethnicity-adjusted yearly cumulative incidence of GDM increased steadily from 5.1% in 1991 to 7.4% in 1997 and leveled off through 2000 (6.9%). DISCUSSION: The observed increase in yearly cumulative incidence of GDM was independent of changes in age and ethnicity of the study population. A true increase in GDM incidence might reflect or contribute to the increases in the prevalence of diabetes and obesity. Coordinated efforts are needed to alter this trend and to prevent chronic diabetes in GDM patients and their offspring. LEVEL OF EVIDENCE: II-2

Gestational Weight Gain and Risk of Gestational Diabetes Mellitus

OBJECTIVE: To estimate the relationship between the rate of gestational weight gain before the 50-g, 1-hour oral glucose challenge test screening for gestational diabetes mellitus (GDM) and subsequent risk of GDM. METHODS: We conducted a nested case–control study (345 women with GDM and 800 women in the control group) within a multiethnic cohort of women delivering between 1996 and 1998 who were screened for GDM at 24–28 weeks of gestation. GDM was diagnosed according to the National Diabetes Data Group plasma glucose cut-offs for the 100-g, 3-hour oral glucose tolerance test. Womens plasma glucose levels, weights, and covariate data were obtained by medical record chart review. RESULTS: After adjusting for age at delivery, race/ethnicity, parity, and prepregnancy body mass index, the risk of GDM increased with increasing rates of gestational weight gain. Compared with the lowest tertile of rate of gestational weight gain (less than 0.27 kg/week [less than 0.60 lb/wk]), a rate of weight gain from 0.27–0.40 kg/wk (0.60–0.88 lb/wk) and 0.41 kg/wk (0.89 lb/wk) or more, were associated with increased risks of GDM (odds ratio 1.43, 95% confidence interval 0.96–2.14; and odds ratio 1.74, 95% confidence interval 1.16–2.60, respectively). The association between the rate of gestational weight gain and GDM was primarily attributed to increased weight gain in the first trimester. The association was stronger in overweight or obese and nonwhite women. CONCLUSION: High rates of gestational weight gain, especially early in pregnancy, may increase a womans risk of GDM. Gestational weight gain during early pregnancy may represent a modifiable risk factor for GDM and needs more attention from health care providers. LEVEL OF EVIDENCE: II

Is Insulin Really a Heart Disease Risk Factor

I n the U.S., the most common cause of death in adults with diabetes is coronary heart disease (1). While this is also true in adults without diabetes, heart disease is at least twice as common in patients with diabetes. The excess risk occurs with both insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). Adults with diabetes are more likely than those without diabetes to have hypertension and dyslipidemia (low levels of high-density lipoprotein, high levels of triglycerides, and small dense low-density lipoprotein [LDL]), but some of the increased risk of heart disease associated with diabetes appears to be independent of these factors.

Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes

IMPORTANCE Studies suggest pioglitazone use may increase risk of cancers. OBJECTIVE To examine whether pioglitazone use for diabetes is associated with risk of bladder and 10 additional cancers. DESIGN, SETTING, AND PARTICIPANTS Cohort and nested case-control analyses among persons with diabetes. A bladder cancer cohort followed 193,099 persons aged 40 years or older in 1997-2002 until December 2012; 464 case patients and 464 matched controls were surveyed about additional confounders. A cohort analysis of 10 additional cancers included 236,507 persons aged 40 years or older in 1997-2005 and followed until June 2012. Cohorts were from Kaiser Permanente Northern California. EXPOSURES Ever use, duration, cumulative dose, and time since initiation of pioglitazone as time dependent. MAIN OUTCOMES AND MEASURES Incident cancer, including bladder, prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectum, and melanoma. RESULTS Among 193,099 persons in the bladder cancer cohort, 34,181 (18%) received pioglitazone (median duration, 2.8 years; range, 0.2-13.2 years) and 1261 had incident bladder cancer. Crude incidences of bladder cancer in pioglitazone users and nonusers were 89.8 and 75.9 per 100,000 person-years, respectively. Ever use of pioglitazone was not associated with bladder cancer risk (adjusted hazard ratio [HR], 1.06; 95% CI, 0.89-1.26). Results were similar in case-control analyses (pioglitazone use: 19.6% among case patients and 17.5% among controls; adjusted odds ratio, 1.18; 95% CI, 0.78-1.80). In adjusted analyses, there was no association with 8 of the 10 additional cancers; ever use of pioglitazone was associated with increased risk of prostate cancer (HR, 1.13; 95% CI, 1.02-1.26) and pancreatic cancer (HR, 1.41; 95% CI, 1.16-1.71). Crude incidences of prostate and pancreatic cancer in pioglitazone users vs nonusers were 453.3 vs 449.3 and 81.1 vs 48.4 per 100,000 person-years, respectively. No clear patterns of risk for any cancer were observed for time since initiation, duration, or dose. CONCLUSIONS AND RELEVANCE Pioglitazone use was not associated with a statistically significant increased risk of bladder cancer, although an increased risk, as previously observed, could not be excluded. The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether they are causal or are due to chance, residual confounding, or reverse causality.

Pregnancy weight gain and risk of neonatal complications: macrosomia, hypoglycemia, and hyperbilirubinemia.

OBJECTIVE: To examine whether pregnancy weight gains outside the Institute of Medicine (IOM) recommendations and rates of maternal weight gain are associated with neonatal complications. METHODS: In a cohort of 45,245 women who delivered singletons at Kaiser Permanente Medical Care Program Northern California in 1996–1998 and who did not have gestational diabetes as of 24–28 weeks of gestation, we conducted a nested case–control study with three case groups: macrosomia (birth weight more than 4,500 g, n=391), neonatal hypoglycemia (plasma glucose less than 40 mg/dL, n=328), and hyperbilirubinemia (serum bilirubin 20 mg/dL or more, n=432) and one control group (n=652). Medical records were reviewed to ascertain the woman’s prepregnancy and predelivery weight. RESULTS: Adjusting for age, race–ethnicity, parity, plasma glucose screening value, and difference in weeks between delivery and time when last weight was measured, women who gained more than recommended by the IOM were three times more likely to have an infant with macrosomia (odds ratio [OR] 3.05, 95% confidence interval [CI] 2.19–4.26), and nearly 1.5 times as likely to have an infant with hypoglycemia (OR 1.38, 95% CI 1.01–1.89), or hyperbilirubinemia (OR 1.43, 95% CI 1.06–1.93) than women whose weight gain was in the recommended range. Women who gained less than the IOM recommendations were less likely than women in the recommended range to have an infant with macrosomia (OR 0.38, 95% CI 0.20–0.70), but equally likely to have an infant with hypoglycemia or hyperbilirubinemia. Similar results were obtained using other means of categorizing weight gain during pregnancy. CONCLUSION: Maternal weight gain above the IOM recommendations was associated with an increased risk of the outcomes studied. LEVEL OF EVIDENCE: II-2

Missed appointments and poor glycemic control: an opportunity to identify high-risk diabetic patients.

Objective.When patients miss scheduled medical appointments, continuity and effectiveness of healthcare delivery is reduced, appropriate monitoring of health status lapses, and the cost of health services increases. We evaluated the relationship between missed appointments and glycemic control (glycosylated hemoglobin or HbA1c) in a large, managed care population of diabetic patients. Research Design and MethodsMissed appointment rate was related cross-sectionally to glycemic control among 84,040 members of the Kaiser Permanente Northern California Diabetes Registry during 2000. Adjusted least-square mean estimates of HbA1c were derived by level of appointment keeping (none missed, 1–30% missed, and >30% missed appointments for the calendar year) stratified by diabetes therapy. ResultsTwelve percent of the subjects missed more than 30% of scheduled appointments during 2000. Greater rates of missed appointments were associated with significantly poorer glycemic control after adjusting for demographic factors (age, sex), clinical status, and health care utilization. The adjusted mean HbA1c among members who missed >30% of scheduled appointments was 0.70 to 0.79 points higher (P <0.0001) relative to those attending all appointments. Patients who missed more than 30% of their appointments were less likely to practice daily self-monitoring of blood glucose and to have poor oral medication refill adherence. ConclusionPatients who underuse care lack recorded information needed to determine level of risk. Frequently missed appointments were associated with poorer glycemic control and suboptimal diabetes self-management practice, are readily ascertained in clinical settings, and therefore could have clinical utility as a risk-stratifying criterion indicating the need for targeted case management.

A Pregnancy and Postpartum Lifestyle Intervention in Women With Gestational Diabetes Mellitus Reduces Diabetes Risk Factors: A feasibility randomized control trial

OBJECTIVE To pilot, among women with gestational diabetes mellitus (GDM), the feasibility of a prenatal/postpartum intervention to modify diet and physical activity similar to the Diabetes Prevention Program. The intervention was delivered by telephone, and support for breastfeeding was addressed. RESEARCH DESIGN AND METHODS The goal was to help women return to their prepregnancy weight, if it was normal, or achieve a 5% reduction from prepregnancy weight if overweight. Eligible participants were identified shortly after a GDM diagnosis; 83.8% consented to be randomly assigned to intervention or usual medical care (96 and 101 women, respectively). The retention was 85.2% at 12 months postpartum. RESULTS The proportion of women who reached the postpartum weight goal was higher, although not statistically significant, in the intervention condition than among usual care (37.5 vs. 21.4%, absolute difference 16.1%, P = 0.07). The intervention was more effective among women who did not exceed the recommended gestational weight gain (difference in the proportion of women meeting the weight goals: 22.5%, P = 0.04). The intervention condition decreased dietary fat intake more than the usual care (condition difference in the mean change in percent of calories from fat: −3.6%, P = 0.002) and increased breastfeeding, although not significantly (condition difference in proportion: 15.0%, P = 0.09). No differences in postpartum physical activity were observed between conditions. CONCLUSIONS This study suggests that a lifestyle intervention that starts during pregnancy and continues postpartum is feasible and may prevent pregnancy weight retention and help overweight women lose weight. Strategies to help postpartum women overcome barriers to increasing physical activity are needed.