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Gestational Diabetes Mellitus Diagnosed With a 2-h 75-g Oral Glucose Tolerance Test and Adverse Pregnancy Outcomes Maria I. Schmidt , MD, PHD 1 , Bruce B. Duncan , MD, PHD 1 , Angela J. Reichelt , MD, PHD 2 , Leandro Branchtein , MD, PHD 2 , Maria C. Matos , MD, PHD 2 , Adriana Costa e Forti , MD, PHD 3 , Ethel R. Spichler , MD, PHD 4 , Judith M.D.C. Pousada , MD, PHD 5 , Margareth M. Teixeira , MD, MS 6 , Tsuyoshi Yamashita , MD 7 and For the Brazilian Gestational Diabetes Study Group 1 Department of Social Medicine, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre 2 Postgraduate Program in Clinical Medicine, Federal University of Rio Grande do Sul, Porto Alegre 3 Department of Clinical Medicine, School of Medicine, Federal University of Ceará, Fortaleza, Ceará 4 Department of Obstetrics and Gynecology, Instituto Fernandes Figueira–Oswaldo Cruz Foundation, Rio de Janeiro 5 Department of Medicine, Medical School, Federal University of Bahia, Salvador, Bahia 6 Department of Medicine, Federal University of Amazonas, Manaus, Amazonas 7 Hospital dos Servidores Públicos do Estado de São Paulo, São Paulo, Brazil Abstract OBJECTIVE —To evaluate American Diabetes Association (ADA) and World Health Organization (WHO) diagnostic criteria for gestational diabetes mellitus (GDM) against pregnancy outcomes. RESEARCH DESIGN AND METHODS —This cohort study consecutively enrolled Brazilian adult women attending general prenatal clinics. All women were requested to undertake a standardized 2-h 75-g oral glucose tolerance test (OGTT) between their estimated 24th and 28th gestational weeks and were then followed to delivery. New ADA criteria for GDM require two plasma glucose values ≥5.3 mmol/l (fasting), ≥10 mmol/l (1 h), and ≥8.6 mmol/l (2 h). WHO criteria require a plasma glucose ≥7.0 mmol/l (fasting) or ≥7.8 mmol/l (2 h). Individuals with hyperglycemia indicative of diabetes outside of pregnancy were excluded. RESULTS —Among the 4,977 women studied, 2.4% (95% CI 2.0–2.9) presented with GDM by ADA criteria and 7.2% (6.5–7.9) by WHO criteria. After adjustment for the effects of age, obesity, and other risk factors, GDM by ADA criteria predicted an increased risk of macrosomia (RR 1.29, 95% CI 0.73–2.18), preeclampsia (2.28, 1.22–4.16), and perinatal death (3.10, 1.42–6.47). Similarly, GDM by WHO criteria predicted increased risk for macrosomia (1.45, 1.06–1.95), preeclampsia (1.94, 1.22–3.03), and perinatal death (1.59, 0.86–2.90). Of women positive by WHO criteria, 260 (73%) were negative by ADA criteria. Conversely, 22 (18%) women positive by ADA criteria were negative by WHO criteria. CONCLUSIONS —GDM based on a 2-h 75-g OGTT defined by either WHO or ADA criteria predicts adverse pregnancy outcomes. ADA, American Diabetes Association GDM, gestational diabetes mellitus OGTT, oral glucose tolerance test RR, relative risk WHO, World Health Organization Footnotes Address correspondence and reprint requests to Maria Inês Schmidt, Av. Luiz Manoel Gonzaga, 630/8, Porto Alegre, RS 90470-280 Brazil. E-mail: bbduncan{at}orion.ufrgs.br . Received for publication 12 October 2000 and accepted in revised form 28 February 2001. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

The major adverse consequences of obesity are associated with the development of insulin resistance (IR) and adiposopathy. The Homeostasis Model Assessment-Adiponectin (HOMA-AD) was proposed as a modified version of the HOMA1-IR, which incorporates adiponectin in the denominator of the index. To evaluate the performance of the HOMA-AD index compared with the HOMA1-IR index as a surrogate marker of IR in women, and to establish the cutoff value of the HOMA-AD. The Brazilian Metabolic Syndrome Study (BRAMS) is a cross-sectional multicenter survey. The data from 1,061 subjects met the desired criteria: 18-65 years old, BMI: 18.5-49.9 Kg/m² and without diabetes. The IR was assessed by the indexes HOMA1-IR and HOMA-AD (total sample) and by the hyperglycemic clamp (n = 49). Metabolic syndrome was defined using the IDF criteria. For the IR assessed by the clamp, the HOMA-AD demonstrated a stronger coefficient of correlation (r = -0.64) compared with the HOMA1-IR (r = -0.56); p < 0.0001. In the ROC analysis, compared with the HOMA1-IR, the HOMA-AD showed higher values of the AUC for the identification of IR based on the clamp test (AUC: 0.844 vs. AUC: 0.804) and on the metabolic syndrome (AUC: 0.703 vs. AUC: 0.689), respectively; p < 0.001 for all. However, the pairwise comparison did not show evidence of superiority for the HOMA-AD in comparison with the HOMA1-IR in the diagnosis of IR and metabolic syndrome (p > 0.05). The optimal cutoff identified for the HOMA-AD for the diagnosis of IR was 0.95. The HOMA-AD index was demonstrated to be a useful surrogate marker for detecting IR among adult women and presented a similar performance compared with the HOMA1-IR index. These results may assist physicians and researchers in determining which method to use to evaluate IR in light of the available facilities.

Aims To determine the prevalence of overweight/obesity and its relationship with metabolic syndrome (MS), fatty liver index (FLI), cardiovascular risk factors (CVRF), and diabetes-related chronic complications (DRCC) in adult patients with type 1 diabetes (T1D). Methods This study was conducted in 14 Brazilian public clinics in ten cities, with 1,390 patients: 802 females (57.7%), 779 (56.0%) Caucasians, aged 33.6 ± 10.8 years, age at diagnosis, 16.2 ± 9.2 years, diabetes duration, 17.4 ± 9.2 years, and HbA1c 8.8 ± 2.0%. Results Overall, 825 patients (59.4%) had normal weight, and 565 had overweight/obesity; ( 429 (30.9%) presented overweight and 136 (9.8%) presented obesity). After adjustments, overweight/obesity was associated with age, family history of overweight/obesity, total daily insulin dose, hypertension, adherence to diet, type of health care insurance, use of metformin, levels of C-reactive protein, triglycerides, uric acid and HDL-cholesterol. These patients also presented a higher prevalence of MS, FLI ≥ 60, and CVRF than patients without overweight/obesity. Overweight/obesity was not associated with DRCC and with HbA1c levels. Conclusions Patients with T1D with overweight/obesity presented traditional risk factors for DRCC, cardiovascular diseases, MS, and non-alcoholic fatty liver disease; most of these risk factors are modifiable and can be avoided with interventions that prevent overweight/obesity.

The purpose of this study is to examine factors and variables associated with hospitalizations in type 2 diabetes mellitus (T2DM). This is a 2-year follow-up study of 145 patients (87 women/58 men), mean age 55.0 ± 3.3 (40 to 60). At baseline, comorbidity severity was evaluated by the Charlson Comorbidity Index (CCI), depressive symptoms by the Beck Depression Inventory (BDI II), sleep quality by the Pittsburgh Sleep Quality Index, daytime sleepiness by the Epworth Sleepiness Scale, and levels of physical activity by the International Physical Activity Questionnaire (IPAQ). Arterial hypertension (74 %), cardiovascular pathology (30 %), and stroke (10 %) were found at baseline. After 2 years, eight cases (6 %) developed a new stroke. At baseline, 70 % (N = 102) of patients had a sedentary life, and 30 % (N = 43) were irregularly active. Two years later, the number of patients with a sedentary life decreased to 52 % (N = 76), and an increase of irregularly active (35 %, N = 51) and active patients (13 %, N = 18; p < 0.005) was observed. Twenty-four individuals (16 %) reported at least one hospitalization. Logistic regression analysis showed that the presence of hypertension and lower physical activity status (IPAQ levels) were predictors of hospitalizations (OR = 0.34, CI 0.14–0.85, p = 0.02); lower physical activity status remained significant in the presence of hypertension (OR = 0.33, CI 0.13–0.84, p = 0.02). In conclusion, higher physical activity status is an independent predictor of lower hospitalizations in T2DM proving that exercising is an important strategy not only to reduce health care costs but also to improve the human burden of hospitalizations for the patients.

Background Gestational diabetes mellitus (GDM), a hyperglycemic state detected during pregnancy, is an established risk factor for diabetes. However, treatment during pregnancy in and of itself is not able to eliminate this risk, and a considerable fraction of women with GDM will develop frank diabetes in the decade following pregnancy. Our aim is to conduct a multicenter randomized controlled trial to investigate the effectiveness of a lifestyle intervention program implemented after a pregnancy complicated by GDM in delaying or preventing the development of type 2 diabetes. Methods Women aged 18 or older identified as having recent GDM are recruited and followed by telephone to assess eligibility for the trial. To be eligible, women must have used insulin during pregnancy or present intermediate hyperglycemia postpartum. Women are encouraged to enter the trial as early as 10 weeks, and are permitted to do so up to 2 years after a pregnancy with GDM. An estimated 740 women will be randomized to either conventional care or to coach-based interventions focused on breastfeeding, weight loss, healthy eating, and increased physical activity, and predominantly delivered by telephone. Women are followed annually to detect new onset diabetes, the primary outcome, and additional secondary outcomes which include reversion to normoglycemia, weight loss, physical activity and fitness, and insulin resistance. Discussion Though previous studies have demonstrated that type 2 diabetes can be delayed or prevented, no study has yet demonstrated the feasibility and effectiveness of similar interventions implemented in the postpartum period for women with recent GDM. If shown to be successful, this approach could become an important means of preventing diabetes in primary care settings. Trial registration ClinicalTrials.gov Identifier: NCT02327286 ; Registered 23 December 2014.

Background Studies on diabetic foot and its complications involving a significant and representative sample of patients in South American countries are scarce. The main objective of this study was to acquire clinical and epidemiological data on a large cohort of diabetic patients from 19 centers from Brazil and focus on factors that could be associated with the risk of ulcer and amputation. Methods This study presents cross sectional, baseline results of the BRAZUPA Study. A total of 1455 patients were included. Parameters recorded included age, gender, ethnicity, diabetes and comorbidity-related records, previous ulcer or amputation, clinical symptomatic score, foot classification and microvascular complications. Results Patients with ulcer had longer disease duration (17.2 ± 9.9 vs. 13.2 ± 9.4 years; p < 0.001), and poorer glycemic control (HbA1c 9.23 ± 2.03 vs. 8.35 ± 1.99; p < 0.001). Independent risk factors for ulcer were male gender (OR 1.71; 95 % CI 1.2–3.7), smoking (OR 1.78; 95 % CI 1.09–2.89), neuroischemic foot (OR 20.34; 95 % CI 9.31–44.38), region of origin (higher risk for those from developed regions, OR 2.39; 95 % CI 1.47–3.87), presence of retinopathy (OR 1.68; 95 % CI 1.08–2.62) and absence of vibratory sensation (OR 7.95; 95 % CI 4.65–13.59). Risk factors for amputation were male gender (OR 2.12; 95 % CI 1.2–3.73), type 2 diabetes (OR 3.33; 95 % CI 1.01–11.1), foot at risk classification (higher risk for ischemic foot, OR 19.63; 95 % CI 3.43–112.5), hypertension (lower risk, OR 0.3; 95 % CI 0.14–0.63), region of origin (South/Southeast, OR 2.2; 95 % CI 1.1–4.42), previous history of ulcer (OR 9.66; 95 % CI 4.67–19.98) and altered vibratory sensation (OR 3.46; 95 % CI 1.64–7.33). There was no association between either outcome and ethnicity. Conclusions Ulcer and amputation rates were high. Age at presentation was low and patients with ulcer presented a higher prevalence of neuropathy compared to ischemic foot at risk. Ischemic disease was more associated with amputations. Ethnical differences were not of great importance in a miscegenated population.

The major adverse consequences of obesity are associated with the development of insulin resistance (IR) and adiposopathy. The Homeostasis Model Assessment-Adiponectin (HOMA-AD) was proposed as a modified version of the HOMA1-IR, which incorporates adiponectin in the denominator of the index. To evaluate the performance of the HOMA-AD index compared with the HOMA1-IR index as a surrogate marker of IR in women, and to establish the cutoff value of the HOMA-AD. For the IR assessed by the clamp, the HOMA-AD demonstrated a stronger coefficient of correlation (r = -0.64) compared with the HOMA1-IR (r = -0.56); p < 0.0001. In the ROC analysis, compared with the HOMA1-IR, the HOMA-AD showed higher values of the AUC for the identification of IR based on the clamp test (AUC: 0.844 vs. AUC: 0.804) and on the metabolic syndrome (AUC: 0.703 vs. AUC: 0.689), respectively; p 0.05). The optimal cutoff identified for the HOMA-AD for the diagnosis of IR was 0.95. The HOMA-AD index was demonstrated to be a useful surrogate marker for detecting IR among adult women and presented a similar performance compared with the HOMA1-IR index. These results may assist physicians and researchers in determining which method to use to evaluate IR in light of the available facilities.

Background In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. Methods MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. Results and conclusions In non-pregnant adults, the recommended HbA 1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA 1c is 6.5–7.5%. When HbA 1c is 7.5–9.0%, dual therapy with metformin plus an SGLT2i and/or GLP- 1 RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA 1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction (< 40%) and glomerular filtration rate (eGFR) > 30 mL/min/1.73 m 2 , metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30–60 mL/min/1.73 m 2 or eGFR 30–90 mL/min/1.73 m 2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP- 1 RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.

Background: In current management of type 2 diabetes (T2DM), cardiovascular and renal prevention have become important targets to be achieved. In this context, a joint panel of four endocrinology societies from Brazil and Portugal was established to develop an evidence-based guideline for treatment of hyperglycemia in T2DM. Methods: MEDLINE (via PubMed) was searched for randomized clinical trials, meta-analyses, and observational studies related to diabetes treatment. When there was insufficient high-quality evidence, expert opinion was sought. Updated positions on treatment of T2DM patients with heart failure (HF), atherosclerotic CV disease (ASCVD), chronic kidney disease (CKD), and patients with no vascular complications were developed. The degree of recommendation and the level of evidence were determined using predefined criteria. Results and conclusions: In non-pregnant adults, the recommended HbA1c target is below 7%. Higher levels are recommended in frail older adults and patients at higher risk of hypoglycemia. Lifestyle modification is recommended at all phases of treatment. Metformin is the first choice when HbA1c is 6.5–7.5%. When HbA1c is 7.5–9.0%, dual therapy with metformin plus an SGLT2i and/or GLP-1RA (first-line antidiabetic agents, AD1) is recommended due to cardiovascular and renal benefits. If an AD1 is unaffordable, other antidiabetic drugs (AD) may be used. Triple or quadruple therapy should be considered when HbA1c remains above target. In patients with clinical or subclinical atherosclerosis, the combination of one AD1 plus metformin is the recommended first-line therapy to reduce cardiovascular events and improve blood glucose control. In stable heart failure with low ejection fraction (< 40%) and glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2, metformin plus an SGLT-2i is recommended to reduce cardiovascular mortality and heart failure hospitalizations and improve blood glucose control. In patients with diabetes-associated chronic kidney disease (CKD) (eGFR 30–60 mL/min/1.73 m2 or eGFR 30–90 mL/min/1.73 m2 with albuminuria > 30 mg/g), the combination of metformin and an SGLT2i is recommended to attenuate loss of renal function, reduce albuminuria and improve blood glucose control. In patients with severe renal failure, insulin-based therapy is recommended to improve blood glucose control. Alternatively, GLP-1RA, DPP4i, gliclazide MR and pioglitazone may be considered to reduce albuminuria. In conclusion, the current evidence supports individualizing anti-hyperglycemic treatment for T2DM.

Background Diabetic retinopathy has a significant impact in every healthcare system. Despite that fact, there are few accurate estimates in the prevalence of DR in Brazil’s different geographic regions, particularly proliferative DR and diabetic macular edema. This study aims to determine the prevalence of diabetic retinopathy in Brazil’s five continental regions and its determinant factors. Methods This multi center, cross-sectional, observational study, conducted between August 2011 and December 2014, included patients with type 1 diabetes from the 5 Brazilian geographic regions (South, Southeast, North, Northeast and Midwest). During a clinical visit, a structured questionnaire was applied, blood sampling was collected and each patient underwent mydriatic binocular indirect ophthalmoscopy evaluation. Results Data was obtained from 1644 patients, aged 30.2 ± 12 years (56.1% female, 54.4% Caucasian), with a diabetes duration of 15.5 ± 9.3 years. The prevalence of diabetic retinopathy was 242 (36.1%) in the Southeast, 102 (42.9%) in the South, 183 (29.9%) in the North and Northeast and 54 (41.7%) in the Midwest. Multinomial regression showed no difference in the prevalence of non-proliferative diabetic retinopathy in each geographic region, although, prevalence of proliferative diabetic retinopathy (p = 0.022), and diabetic macular edema (p = 0.003) was higher in the Midwest. Stepwise analyses reviled duration of diabetes, level of HbA1c and hypertension as independent variables. Conclusions The prevalence of non proliferative diabetic retinopathy in patients with type 1 diabetes was no different between each geographic region of Brazil. The Midwest presented higher prevalence of proliferative diabetic retinopathy and diabetic macular edema. Duration of DM and glycemic control is of central importance to all. Hypertension is another fundamental factor to every region, at special in the South and Southeast. Glycemic control and patients in social and economic vulnerability deserves special attention in the North and Northeast of Brazil.