Foot complications in Type 2 diabetes : an Australian population-based study

Aims To determine the prevalence and risk factors for neuropathy and peripheral vascular disease (PVD) in the Australian diabetic population and identify those at high risk of foot ulceration.

Methods The Australian Diabetes Obesity and Lifestyle study included 11 247 adults aged ≥ 25 years in 42 randomly selected areas of Australia. Neuropathy and PVD were assessed in participants identified as having diabetes (based on self report and oral glucose tolerance test), impaired fasting glucose, impaired glucose tolerance and in a random sample with normal glucose tolerance (total n = 2436).

Results The prevalence of peripheral neuropathy was 13.1% in those with known diabetes (KDM) and 7.1% in those with newly diagnosed (NDM). The prevalence of PVD was 13.9% in KDM and 6.9% in NDM. Of those with diabetes, 19.6% were at risk of foot ulceration. Independent risk factors for peripheral neuropathy were diabetes duration (odds ratio (95% CI) 1.73 (1.33–2.28) per 10 years), height (1.42 (1.08–1.88) per 10 cm), age (2.57 (1.94–3.40) per 10 years) and uric acid (1.59 (1.21–2.09) per 0.1 mmol/l). Risk factors for PVD were diabetes duration (1.64 (1.25–2.16) per 10 years), age (2.45 (1.86–3.22) per 10 years), smoking (2.07 (1.00–4.28)), uric acid (1.03 (1.00–1.06) per 0.1 mmol/l) and urinary albumin/creatinine ratio (1.11 (1.01–1.21) per 1 mg/mmol).

Conclusions The prevalence of neuropathy and PVD was lower in this population than has been reported in other populations. This may reflect differences in sampling methods between community and hospital-based populations. Nevertheless, a substantial proportion of the diabetic population had risk factors for foot ulceration.

Is grand multiparity associated with an increased risk of dysglycaemia?

Aims/hypothesis: We sought to determine the risk of diabetes and IGT/IFG with grand multiparity. Subjects, materials and methods: Women, aged ≥25 years, from the Australian Diabetes, Obesity and Lifestyle Study and the Crossroads Undiagnosed Disease Study (a rural study in Victoria, Australia), participated in a household census (response 67 and 70%, respectively), subsequently attending a biomedical examination that included an oral glucose tolerance test (58% [6198] and 69% [819]). Results: After adjusting for age, obesity and socio-economic status, diabetes, but not IGT/IFG, was less common among women with a parity of 1 to 2 (odds ratio [OR]=0.64 [0.48– 0.84]) and 3 to 4 (OR=0.72 [0.53–0.96]) than in grand multiparous women. This relationship was unrelated to past hysterectomy, use of the oral contraceptive pill or menopausal status. Conclusions/interpretation: Grand multiparity is associated with an increased risk of diabetes but not of IGT/IFG.We postulate that parity accelerates transition from IGT/IFG to diabetes, more than it does transition from normal glucose tolerance to IGT/IFG.

HbA1c as a screening tool for detection of type 2 diabetes: A systematic review

Aim: To assess the validity of glycated haemoglobin A1c (HbA1c) as a screening tool for early detection of Type 2 diabetes.

Methods: Systematic review of primary cross-sectional studies of the accuracy of HbA1c for the detection of Type 2 diabetes using the oral glucose tolerance test as the reference standard and fasting plasma glucose as a comparison.

Results: Nine studies met the inclusion criteria. At certain cut-off points, HbA1c has slightly lower sensitivity than fasting plasma glucose (FPG) in detecting diabetes, but slightly higher specificity. For HbA1c at a Diabetes Control and Complications Trial and UK Prospective Diabetes Study comparable cut-off point of ≥ 6.1%, the sensitivity ranged from 78 to 81% and specificity 79 to 84%. For FPG at a cut-off point of ≥ 6.1 mmol/l, the sensitivity ranged from 48 to 64% and specificity from 94 to 98%. Both HbA1c and FPG have low sensitivity for the detection of impaired glucose tolerance (around 50%).

Conclusions: HbA1c and FPG are equally effective screening tools for the detection of Type 2 diabetes. The HbA1c cut-off point of > 6.1% was the recommended optimum cut-off point for HbA1c in most reviewed studies; however, there is an argument for population-specific cut-off points as optimum cut-offs vary by ethnic group, age, gender and population prevalence of diabetes. Previous studies have demonstrated that HbA1c has less intra-individual variation and better predicts both micro- and macrovascular complications. Although the current cost of HbA1c is higher than FPG, the additional benefits in predicting costly preventable clinical complications may make this a cost-effective choice.

Effects of rosiglitazone on intramyocellular lipid accumulation in Psammomys obesus

Objective: To examine the effects of rosiglitazone in intramyocellular lipid (IMCL) content in diabetic Psammomys obesus using novel electron microscopy technologies.

Background: P. obesus is an unique polygenic model of obesity and type 2 diabetes. Male diabetic P. obesus were treated daily with 5 mg/Kg Rosiglitazone by oral gavage for 14 days. Data were compared with a group of age-matched diabetic P. obesus treated with saline vehicle.

Methods: Assessment of insulin resistance and adiposity were determine before and after the treatment period by oral glucose tolerance test (oGTT) and dual energy X-ray absorptiometry (DEXA) analysis. We used a new scanning electron microscopy technology, (WETSEM) to investigate the effects of rosiglitazone administration on IMCL content, size and distribution in red gastrocnemius muscle.

Results: Rosiglitazone treatment improved glucose tolerance in P. obesus with no difference in the overall body fat content although a significant reduction in subscapular fat mass was observed. Rosiglitazone changed the distribution of lipid droplet size in skeletal muscle. Treated animals tended to have smaller lipid droplets compared with saline-treated controls.

Conclusions: Since smaller IMCL droplets are associated with improvements in insulin sensitivity, we propose that this may be an important mechanism by which rosiglitazone affects glucose tolerance.

Serum 25-Hydroxyvitamin D, calcium intake and risk of type 2 diabetes after 5 years : results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle study)

OBJECTIVE To examine whether serum 25-hydroxyvitamin D (25OHD) and dietary calcium predict incident type 2 diabetes and insulin sensitivity.

RESEARCH DESIGN AND METHODS A total of 6,537 of the 11,247 adults evaluated in 1999–2000 in the Australian Diabetes, Obesity and Lifestyle (AusDiab) study, returned for oral glucose tolerance test (OGTT) in 2004–2005. We studied those without diabetes who had complete data at baseline (n = 5,200; mean age 51 years; 55% were women; 92% were Europids). Serum 25OHD and energy-adjusted calcium intake (food frequency questionnaire) were assessed at baseline. Logistic regression was used to evaluate associations between serum 25OHD and dietary calcium on 5-year incidence of diabetes (diagnosed by OGTT) and insulin sensitivity (homeostasis model assessment of insulin sensitivity [HOMA-S]), adjusted for multiple potential confounders, including fasting plasma glucose (FPG).

RESULTS During the 5-year follow-up, 199 incident cases of diabetes were diagnosed. Those who developed diabetes had lower serum 25OHD (mean 58 vs. 65 nmol/L; P < 0.001) and calcium intake (mean 881 vs. 923 mg/day; P = 0.03) compared with those who remained free of diabetes. Each 25 nmol/L increment in serum 25OHD was associated with a 24% reduced risk of diabetes (odds ratio 0.76 [95% CI 0.63–0.92]) after adjusting for age, waist circumference, ethnicity, season, latitude, smoking, physical activity, family history of diabetes, dietary magnesium, hypertension, serum triglycerides, and FPG. Dietary calcium intake was not associated with reduced diabetes risk. Only serum 25OHD was positively and independently associated with HOMA-S at 5 years.

CONCLUSIONS Higher serum 25OHD levels, but not higher dietary calcium, were associated with a significantly reduced risk of diabetes in Australian adult men and women.

Insulin sensitivity in response to a single resistance exercise session in apparently healthy individuals

BACKGROUND: Regular resistance exercise completed for a number of weeks has been shown to increase insulin sensitivity and reduce the risk of diabetes-related complications. However, the acute responses to resistance exercise have not been adequately investigated in relation to training frequency.
AIM: To investigate the changes to insulin sensitivity in apparently healthy individuals following a single session of unaccustomed resistance exercise.
SUBJECTS AND METHODS: Ten sedentary, apparently healthy individuals performed a baseline oral glucose tolerance test and maximal strength testing. Participants then performed a single session of moderate-high intensity resistance exercise which was followed by 4 consecutive days of oral glucose tolerance testing, for which participants replicated their initial diet. Mean estimated insulin sensitivity change scores from baseline values and their 95% confidence intervals were compared to the previously determined values for a clinically meaningful change.
RESULTS: Two participants were identified as having hyperinsulinemia and their data were therefore removed from the main analysis. There was a clinically meaningful increase in insulin response (mean >7237 pmol·l⁻¹·120 min⁻¹) on all days following the exercise session and a clinically meaningful increase in glucose response (mean >81 mmol·l⁻¹·120 min⁻¹) on only the 3rd day following exercise. These changes suggest a potentially adverse short-term effect. Additionally, the 2 individuals with hyperinsulinemia displayed more extreme results.
CONCLUSION: These results suggest that insulin sensitivity may be impaired following a single session of unaccustomed resistance exercise for approximately 4 days in healthy untrained, older individuals. Further research is required for individuals with hyperinsulinemia

Primary prevention of gestational diabetes for women who are overweight and obese : a randomised controlled trial

Background: Gestational Diabetes Mellitus (GDM) has well recognised adverse health implications for the  mother and her newborn that are both short and long term. Obesity is a significant risk factor for developing GDM and the prevalence of obesity is increasing globally. It is a matter of public health importance that clinicians have evidence based strategies to inform practice and currently there is insufficient evidence regarding the impact of dietary and lifestyle interventions on improving maternal and newborn outcomes. The primary aim of this study is to measure the impact of a telephone based intervention that promotes positive lifestyle modifications on the incidence of GDM. Secondary aims include: the impact on gestational weight gain; large for gestational age babies; differences in blood glucose levels taken at the Oral Glucose Tolerance Test (OGTT) and selected factors relating to self-efficacy and psychological wellbeing. 

Importância dos ensaios para medida do hormônio de crescimento na determinação da atividade da acromegalia

A dosagem do GH no soro é essencial para confirmar ou excluir o seu excesso. Na acromegalia, a ausência de critérios clínicos suficientemente sensíveis para monitorizar o sucesso do tratamento faz com que o GH sérico seja o procedimento de escolha e, para isso, é essencial que a sua dosagem seja realizada de forma confiável, capaz de permitir interpretações uniformes. Vários critérios hormonais têm sido propostos para caracterizar remissão da acromegalia, incluindo níveis séricos de GH randômico inferior a 2,5 μg/l, nadir de GH durante o teste de tolerância oral a glicose inferior a 1,0 μg/l e IGF-I normal para sexo e idade. A importância do tratamento adequado consiste na possibilidade de reverter a mortalidade prematura da acromegalia através da diminuição dos níveis de GH para valores menores que 2,5 μg/l. Com o surgimento de ensaios ultra-sensíveis para medida do GH, tornaram-se necessários critérios mais estritos para determinar cura ou remissão da doença. Nesta revisão, descreveremos aqui as modificações decorrentes da evolução dos ensaios, as conseqüências nos resultados de GH e os pontos de corte propostos na literatura para caracterização da atividade e remissão da acromegalia.

Índices de obesidade central e fatores de risco cardiovascular na síndrome dos ovários policísticos

Fundamento: A obesidade abdominal apresenta elevada prevalência em mulheres com síndrome dos ovários policísticos (SOP) e está associada a um aumento do risco cardiovascular. Objetivo: Verificar a acurácia da circunferência da cintura (CC), da relação cintura-quadril (RCQ), da relação cinturaestatura (RCEST) e do índice de conicidade (índice C), no que se refere à detecção de fatores de risco cardiovascular (FRCV) em mulheres com SOP. Métodos: Por meio de estudo transversal, foram alocadas 102 mulheres (26,5 ± 5 anos) com diagnóstico de SOP, de acordo com o consenso de Rotterdam. O colesterol total (CT), os triglicerídeos (TG), o LDL-colesterol (LDL-C), o HDLcolesterol (HDL-C), a glicemia de jejum, a glicemia após teste oral de tolerância à glicose (TOTG) e a pressão arterial (PA) foram avaliados em todas as pacientes, além das variáveis antropométricas. Resultados: A relação cintura-estatura foi o marcador que apresentou correlações positivas significativas com o maior número de FRCV (PA, TG e glicemia após TOTG), destacando-se ainda a correlação negativa com HDL-C. Todos os marcadores antropométricos avaliados se correlacionaram positivamente com PA, enquanto CC e RCQ apresentaram correlação positiva também com TG. No tocante à acurácia para detecção de FRCV, os indicadores antropométricos considerados apresentaram taxas de sensibilidade superiores a 60%, com destaque para a RCEST, que apresentou sensibilidade superior a 70%. Conclusão: A RCEST demonstrou ser o indicador antropométrico com a melhor acurácia para a predição de FRCV. Nesse sentido, propõe-se a inclusão desse parâmetro de fácil mensuração na avaliação clínica para o rastreamento de mulheres com SOP e FRCV----------------------ABSTRACT Background: Women with polycystic ovary syndrome (PCOS) present a high prevalence of abdominal obesity, which is associated with an increased cardiovascular risk. Objective: To verify the accuracy of the waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) and the conicity index (CI) in the detection of cardiovascular risk factors (CVRF) in women with PCOS. Methods: The present transversal study allocated 102 women (26.5 ± 5 years) with a diagnosis of PCOS, according to the Rotterdam criteria. Total cholesterol (TC), triglycerides (TG), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), fasting glucose, glucose after the oral glucose tolerance test (OGTT) and blood pressure (BP) were evaluated in all patients, in addition to the anthropometric variables. Results: The WHtR was the marker that presented significant positive correlations with the highest number of CVRF (BP, TG and post-OGTT glucose), whereas there was a negative correlation with HDL-C. All the evaluated anthropometric markers were positively correlated with BP, whereas WC and WHR also presented a positive correlation with TG. Regarding the accuracy for the detection of CVRF, the anthropometric markers presented a sensibility > 60%, especially the WHtR, which had a sensibility > 70%. Conclusion: The WHtR showed to be the most accurate anthropometric indicator for the prediction of CVRF. In this sense, we propose the inclusion of this easily-measured parameter in the clinical assessment for the screening of women with PCOS and CVRF

Sobrepeso na adolescência de filhos de mães que tiveram distúrbios glicêmicos na gestação

OBJETIVO: Observar se diferentes graus de hiperglicemia durante a gestação determinam diferentes freqüências de obesidade e suas comorbidades na adolescência dos filhos. MÉTODOS: Participaram 73 filhos distribuídos em três grupos, segundo a tolerância à glicose materna: G1 (n = 27) teste oral de tolerância à glicose (TOTG) e glicemia diária (GD) normais; G2 (n = 23) TOTG normal e GD elevada; G3 (n = 23) TOTG e GD alterados (diabetes melito ges tacional - DMG). Todos foram submetidos à avaliação clínica (antropometria), a um questionário (dados neonatais, hábitos alimentares) e a dosagem basal de glicose e perfil lipídico sérico. A comparação entre os grupos foi feita por análise de variância e teste de Goodman. RESULTADOS: As mães G3 apresentaram glicemia de jejum (GJ) e GD mais elevadas que as G2 e G1 (GJ: 98 ± 10 versus 83 ± 5 versus 78 ± 10 mg/dL; GD: 104 ± 12 versus 93 ± 7 versus 85 ± 9 mg/dL, respectivamente; p < 0,001). As mães G2 apresentaram GD mais elevada que as G1 (93 ± 7 versus 85 ± 9 mg/dL; p < 0,001). O peso de nascimento (PN) dos filhos G3 foi mais elevado que o dos G2 e G1 (3.667 ± 527 versus 3.167 ± 565 e 3.282 ± 401 g, respectivamente; p < 0,05). Os filhos G3 apresentaram maior freqüência de sobrepeso que os G1 (52,2 versus 14,8%; p < 0,05). CONCLUSÕES: Mães com DMG, apresentando GJ e GD elevadas, têm filhos com maior PN e maior freqüência de sobrepeso na adolescência. Esses filhos precisam ser acompanhados desde a infância.

Avaliação quanto à presença de microalbuminúria e hiperfiltração glomerular no estágio de tolerância à glicose diminuída

Na fase de tolerância à glicose diminuída (TGD) já estão presentes vários distúrbios metabólicos característicos do diabetes mellitus tipo 2 e fatores de risco que predispõem à vasculopatia. Nosso objetivo foi o de verificar se indivíduos de nossa população, com TGD e normotensos, apresentam elevação da excreção urinária de albumina (EUA) e da depuração de creatinina (D Cr). Teste oral de tolerância à glicose padrão com dosagem de insulina foi realizado, classificando os participantes em dois grupos: com TGD e com tolerância à glicose normal (TGN). Urina do período noturno foi utilizada para a determinação da EUA (imunoturbidimetria) e da D Cr. Os dois grupos não diferiram quanto à EUA e à D Cr. A freqüência de microalbuminúria foi de 21,1 e 3,3%, respectivamente, para os grupos com TGD e TGN (NS). Concluímos que, nesta amostra da população brasileira, indivíduos com TGD, normotensos e com resistência à insulina não apresentaram microalbuminúria e hiperfiltração glomerular.

Ocorrência de diabetes melito em mulheres com hiperglicemia em gestação prévia

OBJETIVO: Verificar a freqüência com que ocorria intolerância à glicose (diabetes melito e tolerância à glicose diminuída) em mulheres cuja gestação foi acompanhada e avaliada quanto à tolerância à glicose. MÉTODOS: Num período de até 12 anos da gestação-alvo, de um total de 3.113 gestantes acompanhadas em um serviço de obstetrícia, 551 foram selecionadas por meio de um processo randômico, proporcional à representação dos grupos. Foram avaliadas 529, assim constituídas: 250 normotolerantes à glicose, grupo IA; 120 com hiperglicemia diária, grupo IB; 72 com o teste oral de tolerância à glicose alterado, grupo IIA; e 87 com o teste oral de tolerância à glicose alterado e hiperglicemia diária, grupo IIB. A avaliação constava da medida da glicemia de jejum, que entre 110 e 125 mg/dL, era seguida pelo teste oral de tolerância à glicose. RESULTADOS: A freqüência de ocorrência de diabetes foi 1,6, 16,7, 23,6 e 44,8% nos grupos IA, IB, IIA e IIB, respectivamente (IA <[IB=IIA]teste oral de tolerância à glicose alterado durante a gestação são igualmente eficazes em predizer o futuro desenvolvimento de diabetes materno; quando ambos os testes são alterados, tal prognóstico se agrava significativamente.

Vascular endothelial growth factor (VEGF) and VEGF-receptor expression in placenta of hyperglycemic pregnant women

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Mild gestational hyperglycaemia as a risk factor for metabolic syndrome in pregnancy and adverse perinatal outcomes

Objective The aims of this study were to evaluate the prevalence of metabolic syndrome (MS) in a cohort of pregnant women with a wide range of glucose tolerance, pre-pregnancy risk factors for MS during pregnancy and the effects of MS in the occurrence of adverse perinatal outcomes.Research Design and Methods One hundred and thirty six women with positive screening for gestational diabetes (GDM) were classified by two diagnostic methods: glycaemic profile and 100 g oral glucose tolerance test (OGTT) as normoglycaemic, mild gestational hyperglycaemic, GDM, and overt GDM. Markers of insulin resistance were measured between 24-28 and 36th week of gestation, and 6 weeks after delivery.Results The prevalence of MS was 0; 20.0; 23.5 and 36.4% in normoglycaemic, mild hyperglycaemic, GDM and overt GDM groups, respectively. Previous history of GDM with or without insulin use, body mass index (BMI) >= 25, hypertension, family history of diabetes in first-degree relatives, non-Caucasian ethnicity, history of prematurity and polyhydramnios were statistically significant pre-pregnancy predictors for MS in the index pregnancy, that by its turn increased the occurrence of adverse perinatal outcomes (p = 0.01).Conclusions The prevalence of MS increases with the worsening of glucose tolerance and is an independent predictor of adverse perinatal outcomes; impaired glycaemic profile identifies pregnancies with important metabolic abnormalities that are linked to the occurrence of adverse perinatal outcomes even in the presence of a normal OGTT, in patients that are not currently classified as having GDM. Copyright (C) 2008 John Wiley & Sons, Ltd.

Histopathological placental lesions in mild gestational hyperglycemic and diabetic women

Objective: To investigate and compare the incidence of histopathological placental lesions in mild gestational hyperglycemia, gestational diabetes and overt diabetes at term and preterm gestation.Research design and methods: One-hundred-and-thirty-one placental samples were collected from Diabetes mellitus (DM) positive screened patients. Two diagnostic tests, glycemic profile and 100 g oral glucose tolerance test (OGTT) in parallel identified 4 groups normoglycemic, mild gestational hyperglycemia (MGH), gestational DM (GDM) or overt DM (DM). Placental tissue specimens and sections from 4 groups were obtained by uniform random sampling and stained with hematoxylin-eosin.Results: Placentas from MGH group presented 17 types of histopathological change and higher rates of syncytial nodes and endarteritis. GDM placentas presented only nine types of histopathological change, high rates of dysmaturity, low rates of calcification and no syncytial nodes. Overt DM placentas showed 22 types of histopathological change, 21 of which were present in the preterm period. There were histopathological similarities between MGH and DM placentas, but the former exhibited a higher incidence of endarteritis, which has been described as a post-mortem phenomenon.Conclusion: Our results confirmed that the distinct placental changes associated with DM and MGH depend on gestational period during which the diabetic insult occurs. It may reasonably be inferred that subclinical maternal hyperglycemia during pregnancy, as showed in MGH group, is responsible for increased placental endarteritis, a postmortem lesion in the live fetus.