The impact of fetal sex on risk factors for gestational diabetes and related adverse pregnancy outcomes.

AIMS: To investigate whether fetal sex affects the impact of classical GDM risk factors on the diagnosis of gestational diabetes (GDM) as well as on related adverse pregnancy outcomes. METHODS: This retrospective observational study concerned 206,917 singleton live births born to 170,126 women aged 15-45 over the years 2010-2018 in Tuscany, Italy. GDM was identified by administrative data-sources in 21,613 pregnancies (10.5%) by assessing, through multiple logistic models, whether fetal sex modified the risk of GDM driven by maternal risk factors, and whether it modified the risk of adverse outcomes such as prematurity (birth ≤ 37th gestational week), large for gestational age (LGA), unplanned caesarean sections, or 5-min-Apgar-index ≤ 7 in pregnancies with GDM. RESULTS: GDM was diagnosed in 21,613 pregnancies (10.5%). Male fetal sex predicted a higher adjusted risk of GDM: OR = 1.05(95% CI: 1.01-1.07); p < 0.0009. In pregnancies with female sex, pre-pregnancy obesity amplified the risk of GDM: OR = 1.09(95% CI: 1.01-1.19); p = 0.04. In pregnancies with GDM, carrying a female fetus increased the risk of LGA associated with pregestational obesity OR = 1.45(95% CI: 1.15-1.81); p = 0.001, and in primiparous pregnancies, it protected mothers from the risk of unplanned caesarean sections OR = 0.80(95%CI: 0.67-0.92); p = 0.001. CONCLUSIONS: While male fetal sex is associated with rise in the risk of GDM, giving birth to a girl amplifies the excess GDM risk driven by pregestational obesity, thus increasing the risk of LGA in pregnancies with GDM. Additionally, female fetal sex in pregnancies with GDM seems to protect from the risk of unplanned caesarean sections in primiparous pregnancies.

The Role of New Technological Opportunities and the Need to Evaluate the Activities Performed in the Prevention of Diabetic Foot with Exercise Therapy.

The diabetic foot (DF) is one of the most feared conditions among chronic complications of diabetes, which affects a growing number of patients. Although exercise therapy (ET) has always been considered a pillar in the treatment of patients at risk of DF it is not usually used. Several causes can contribute to hindering both the organization of ET protocols for Diabetes Units and the participation in ET programs for patients at different levels of risk of foot ulceration. The risk of favoring the occurrence of ulcers and the absence of clear evidence on the role played by ET in the prevention of ulcers could be considered among the most important causes leading to the low application of ET. The increased availability of new technologies and in particular of systems and devices equipped with sensors can enable the remote monitoring and management of physical activity performed by patients. Consequently, they can become an opportunity for introducing the systematic use of ET for the treatment of patients at risk. Considering the complexity of the clinical conditions that patients at risk or with diabetic foot ulcer can show, the evaluation of how patients perform the ET proposed can consequently be very important. All this can contribute to improving the treatment of patients and avoiding possible adverse effects. The aim of this brief review was to describe that the use of new technologies and the assessment of the execution of the ET proposed allows an important step forward in the management of patients at risk.

Gender Difference in the Risk of Adverse Outcomes After Diabetic Foot Disease: A Mini-Review.

Diabetic foot disease (DFD) is a complication of diabetes mellitus, characterized by multiple pathogenetic factors, bearing a very high burden of disability as well as of direct and indirect costs for individuals or healthcare systems. A further characteristic of DFD is that it is associated with a marked risk of subsequent hospitalizations for incident cardiovascular events, chronic renal failure or of allcause mortality. Additionally, DFD is strongly linked to the male sex, being much more prevalent among men. However, even if DFD mainly affects males, several past reports suggest that females are disadvantaged as regards the risk of subsequent adverse outcomes. This review aims to clarify this point, attempting to provide an explanation for this apparent oddity: being DFD a typically male complication of diabetes but, seemingly, with a greater load of subsequent consequences for females.

Assessment of cutaneous microcirculation by laser Doppler flowmetry in type 1 diabetes.

BACKGROUND: The burden of type 1 diabetes (T1D) is growing worldwide, stressing the requirement to limit the threat of its long-term complications. In this regard, the development of methods for the early diagnosis and non-invasive monitoring of vascular abnormalities is widely recognized as one of the greatest priorities of the clinical research in this field. OBJECTIVE: To assess the deterioration of physiological properties extracted from laser Doppler flowmetry (LDF) signals of microvascular perfusion and, secondly, to investigate their association with the quality of long-term metabolic control. METHODS: Microvascular perfusion was recorded at the hallux of 63 control subjects and 47 T1D patients, whose glycaemic control was characterized in terms of the annual average levels of glycosylated haemoglobin (HbA1c). Pulse Decomposition Analysis was applied to the LDF data, in order to derive non-invasive markers of vascular stiffness based on a multi-Gaussian representation of the peripheral pulse waveforms; furthermore, wavelet transform analysis was used to evaluate the microvascular myogenic vasomotion and, finally, a physiological model of the reactive hyperaemia to a local thermal stimulus at 43 was used to test the integrity of the neurovascular pathways. RESULTS: Compared to the control group, T1D patients showed a lower microvascular perfusion at baseline, and a larger vasodilatory reserve upon local heating, but no significant difference in myogenic activity. Moreover, the results of the PDA carried out on the LDF pulse waves, indicate the presence of a significant strong relation between large artery stiffness and the overall loss of glycaemic control over the past year.

Tapentadol Prolonged Release Reduces the Severe Chronic Ischaemic Pain and Improves the Quality of Life in Patients with Type 2 Diabetes.

This study has been performed in diabetic type 2 patients with pain due to peripheral artery disease (PAD) in order to evaluate the efficacy and tolerability of tapentadol prolonged release (PR). Methods. 25 patients with type 2 diabetes (13 F and 12 M) were admitted in the study. The evaluation of the analgesic efficacy of tapentadol PR was based on both the assessment of the intensity of the pain (NRS scale from 0 to 10) and the nature of the pain (DN4 questionnaire) and on assessment of the patient's quality of life and state of health (SF-12 Health Survey). Study duration was 3 months: a baseline visit and follow-up included visits after 1 week, 1 month, 2 months, and 3 months. Results. At the beginning of the study, the mean intensity of the pain was 7.88 ± 1.17 on the NRS scale and at visit 2 it reduced in a statistically significant way; at the end of the treatment with tapentadol PR, the mean intensity was 2.84 points on the NRS scale. Conclusion. In type 2 diabetic patients with chronic severe pain due to PAD, tapentadol PR reduced pain intensity, improving the quality of life.

History, Prevalence and Assessment of Limited Joint Mobility, from Stiff Hand Syndrome to Diabetic Foot Ulcer Prevention: A Narrative Review of the Literature.

BACKGROUND: Limited Joint Mobility (LJM) is a dreaded complication of Diabetes Mellitus (DM). During the last half century, LJM has been studied in patients of different age because it has been considered useful for the monitoring of a patient's condition and for the prevention of vascular disease and diabetic foot. OBJECTIVES: The main aims of this review are to describe the relationship between DM and joint mobility as well as its prevalence and assessment. We have also investigated the role of LJM in the development of diabetic foot ulcers. METHODOLOGY: An in-depth literature search was conducted to identify studies that examined the prevalence and characteristics of LJM in patients with DM of different types, age, durations and chronic complications. RESULTS: Many factors (therapy improvements, population characteristics and different evaluation methods) concur to hinder an exact assessment of the prevalence of LJM. However, it has been confirmed that LJM is widespread among patients with DM and may affect more than two-thirds of them in addition to being a major risk factor for foot ulcer. Its role in the monitoring of a patient's condition is also important for the definition of risk thresholds such as in patients with diabetic foot. The efficacy of exercise therapy for the treatment of LJM, also in patients at risk of foot ulcer, has not been discussed. CONCLUSION: Difficulties encountered in the definition of the prevalence of LJM may hinder its study and the establishment of preventive interventions. However, LJM plays a key role in the monitoring of patients, especially those at risk for ulcer.

Hospitalization for Charcot neuroarthropathy in diabetes: A population study in Italy.

AIMS: To provide data on hospitalization and incidence rates of Charcot neuroarthropathy (CN) and its relation to lower limbs' amputations/revascularizations in population with diabetes of Italy as well as of one of its regions (Tuscany). METHODS: Hospitalizations with CN diagnosis (codes ICD-9-CM: 7130, 7135, 7138) have been recorded in people with diabetes over years 2003-2013 in Italy and 2008-2015 in Tuscany. Amputations, peripheral vascular disease, revascularizations and infections were likewise evaluated. RESULTS: Between 2003 and 2013 CN hospitalizations were very infrequent in Italy ranging between 14×100,000 and 11×100,000 patients with diabetes. In Tuscany they declined to a minimum of 7×100,000 patients in 2015, after a previous increase to a maximum of 22×100,000 (p=NS for both). Yearly CN incidence remained constant in Italy, declining in Tuscany to a minimum of 3.4×100,000 diabetic patients in 2015 (p=0.047). CN patients were younger and with longer length of hospital stay than those with non-Charcot diabetic foot (p<0.05 for both). Amputation and infection rates were manifold higher in CN patients than in those with non-Charcot diabetic foot, while the revascularization rate was similar in both. CONCLUSIONS: Over last decade, in Italy and Tuscany yearly CN incidence and hospitalization rates concerned only a small percentage of patients, remaining constant over years and declining in Tuscany in the last couple of years. CN was significantly associated to younger age, longer hospital stay and greater risk of amputations and infections while the need of revascularization was similar to that of non-Charcot diabetic foot.

Prescribing exercise for prevention and treatment of gestational diabetes: review of suggested recommendations.

Exercise has been proved to be safe during pregnancy and to offer benefits for both mother and fetus; moreover, physical activity may represent a useful tool for gestational diabetes prevention and treatment. Therefore, all women in uncomplicated pregnancy should be encouraged to engage in physical activity as part of a healthy lifestyle. However, exercise in pregnancy needs a careful medical evaluation to exclude medical or obstetric contraindications to exercise, and an appropriate prescription considering frequency, intensity, type and duration of exercise, to carefully balance between potential benefits and potential harmful effects. Moreover, some precautions related to anatomical and functional adaptations observed during pregnancy should be taken into consideration. This review summarized the suggested recommendations for physical activity among pregnant women with focus on gestational diabetes.

Taurine Transporter Gene Expression in Mononuclear Blood Cells of Type 1 Diabetes Patients.

BACKGROUND: Taurine transporter gene expression (RNA-TauT) has a role in retinal cell function and is modulated in vitro and in vivo by hyperglycemia and/or oxidative stress. This study was aimed at testing whether RNA-TauT gene expression is modified in blood mononuclear peripheral cells (MPCs) of type 1 diabetic patients, is related to plasma markers of oxidative stress or endothelial dysfunction, or, finally, is related to presence of retinopathy. METHODS: RNA-TauT was measured in MPCs by real-time PCR-analysis in 35 type 1 diabetic patients and in 33 age- and sex-matched controls, additionally measuring plasma and cell taurine and markers of oxidative stress and endothelial dysfunction. RESULTS: RNA-TauT, expressed as 2(-ΔΔCt), was significantly higher in MPCs of type 1 diabetic patients than in controls [median (interquartile range): 1.32(0.31) versus 1.00(0.15); P = 0.01]. In diabetic patients RNA-TauT was related to HbA1c (r = 0.42; P = 0.01) and inversely to plasma homocysteine (r = -0.39; P = 0.02) being additionally significantly higher in MPCs of patients without retinopathy [(n = 22); 1.36(0.34)] compared to those with retinopathy [(n = 13); 1.16(0.20)], independently from HbA1c or diabetes duration. CONCLUSIONS: RNA-TauT gene expression is significantly upregulated in MPCs of type 1 diabetes patients and is related to HbA1c levels and inversely to plasma homocysteine. Finally, in diabetes patients, RNA-TauT upregulation seems to be blunted in patients with retinopathy independently of their metabolic control or longer diabetes duration.

The role of joint mobility in evaluating and monitoring the risk of diabetic foot ulcer.

AIMS: Evaluation of how ankle joint mobility (AJM) can be useful in the identification of patients with diabetes at risk of foot ulcer (FU). METHODS: Plantar and dorsal flexion of foot were evaluated using an inclinometer in 87 patients (54 type 2 and 33 type 1), and 35 healthy sex- and age-matched control subjects. Patients with diabetes were followed up for diagnosis of FU over the next 8 years and subsequently, patients were subdivided into: those without a history of FU (18 type 1 and 33 type 2), those who had a history of FU detected before baseline evaluation (14 type 2) and those who had history of first ulceration detected by the 8th year of the evaluation period (7 type 2). RESULTS: Aging and diabetes caused a significant reduction in mobility of each of the movements investigated (p<0.001), whereas after adjusting for the confounding effect of age, diabetes specifically reduced plantar flexion (p<0.0001). AJM was significantly lower in those with history of previous FU compared to all the other groups (p<0.001). The first ulceration was detected in the same foot presenting lower AJM in 17 of the 22 subjects with diabetes with history of ulcer (77.27%). CONCLUSIONS: Diabetes and aging reduce AJM although diabetes seems to reduce plantar flexion to a more specific extent. Reduced AJM is mostly associated with a previous history of FU. The evaluation of AJM is a valid and reliable ulcer risk scale that indicates which foot is at higher ulcer risk.

Diabetic foot prevention: the role of exercise therapy in the treatment of limited joint mobility, muscle weakness and reduced gait speed.

OBJECTIVE: It is well known that limited joint mobility of the ankle and foot level, impaired muscular performance and reduced gait speed are risk factors for ulceration in diabetic foot. The aim of this study was to evaluate the effect of an experimental protocol of exercise therapy on joint mobility, muscular strength and gait speed in a group of long-term diabetic subjects. METHODS: The protocol consisted of a 12-week supervised training program; both joint mobility and muscular strength at the ankle were measured before and after exercise therapy respectively by an inclinometer and isometric dynamometers in 26 diabetic subjects and compared to 17 healthy controls. RESULTS: Ankle joint mobility of plantar flexion was reduced about 36% and dorsal flexion by about 23% in diabetic subjects compared to controls (p < 0.001), but significantly increased after exercise therapy (p < 0.001 for both). Ankle muscular strength in plantar flexion was reduced by about 51% and in dorsal flexion by 30% in diabetic patients compared to controls, but these also significantly increased after exercise therapy (p < 0.001). Consequently, patients' walking speed increased after exercise therapy by 0.28 m/s (p < 0.001). CONCLUSION: A 12-week supervised program of exercise therapy significantly improves joint mobility, muscular performance and walking speed in diabetic patients--thus limiting one of the pathogenic factors of diabetic foot and potentially preventing disability.

Effect of diabetes on hospitalization for ischemic stroke and related in-hospital mortality: a study in Tuscany, Italy, over years 2004-2011.

BACKGROUND: Incidence of ischemic stroke and associated in-hospital mortality is decreasing in Western populations, while the prevalence of diabetes, a well-known risk factor for ischemic stroke, is progressively rising. This study was aimed at evaluating the effect of diabetes on ischemic stroke hospitalization and in-hospital mortality after ischemic stroke. METHODS: Discharges with diagnosis of ischemic stroke were identified in a database containing all hospitalizations of resident population of Tuscany, Italy, over years 2004-2011. Cases with diabetes were identified through specific drug prescriptions, official certifications or previous hospital diagnosis. Rates of annual ischemic stroke incidence and related in-hospital mortality were separately calculated for gender and age class, in subjects with and without diabetes. RESULTS: Sixty-five thousand one hundred sixty-five hospital discharges with ischemic stroke diagnosis were identified. Diabetes was associated with increased risk of stroke odds ratio(95% confidence interval):1.31(1.28-1.34) in men and 1.24(1.21-1.37) in women. Diabetic women, compared with men, had a higher in-hospital mortality risk after ischemic stroke (odds ratio:1.32; 1.06-1.64), whereas in non-diabetic subjects, there was no difference between genders. Incidence of ischemic stroke has declined in non-diabetic subjects, except for women aged ≤70 years; a similar reduction was observed for in-hospital mortality. Among diabetic patients, conversely, annual incidence of ischemic stroke rose by 3% in the elderly people (>70 years), and annual mortality trend remained unchanged. CONCLUSIONS: In the last decade, the incidence of ischemic stroke and of related in-hospital mortality declined in persons without diabetes, while increasing among diabetic patients of advanced age. Women with diabetes, compared with men, had a higher in-hospital mortality risk.

Lower extremity amputations in persons with and without diabetes in Italy: 2001-2010.

OBJECTIVE: To analyze hospitalization for lower extremity amputations (LEAs) and amputee rates in persons with and without diabetes in Italy. RESEARCH DESIGN AND METHODS: All patients with LEAs in the period 2001-2010 were identified analyzing the National Hospital Discharge Record database. For each year, amputee and hospitalization rates for LEAs were calculated either for persons with diabetes or without. Time trend for major and minor amputations were analysed. RESULTS: From 2001 to 2010 a mean annual number of 11,639 individuals underwent a lower extremity amputation: 58.6% had diabetes accounting for 60.7% of total hospitalizations. In 2010, the crude amputee rate for LEAs was 20.4 per 100,000 inhabitants: 247.2 for 100.000 persons with diabetes, and 8.6 for those without diabetes. Having diabetes was associated to an increased risk of amputation (Poisson estimated RR 10.9, 95%CI 9.4-12.8). Over the whole period, a progressive reduction of amputee rates was observed for major amputations either among persons with diabetes (-30.7%) or without diabetes (-12.5%), while the rates of minor amputations increased progressively (+22.4%) among people without diabetes and were nearly stable in people with diabetes (-4.6%). A greater number of minor amputations were performed among persons with than without diabetes: in 2010, the minor-to-major ratio among persons with diabetes (2.5) was more than twice than in those without diabetes (1.0). CONCLUSIONS: The nationwide analyses confirm a progressive reduction of hospitalization and amputee rates for major LEAs, suggesting an earlier and more diffuse approach aimed at limb salvage.

Gender difference in response predictors after 1-year exenatide therapy twice daily in type 2 diabetic patients: a real world experience.

PURPOSE: To investigate whether gender affects therapeutic response by exenatide twice a day (BID) in type 2 diabetes by using a database concerning patients monitored by five outpatient clinics in Tuscany, Italy. PATIENTS AND METHODS: We considered a cohort of 315 (154 male/161 female) patients experiencing therapeutic failure while on oral therapy (metformin, or combination therapy metformin + sulphonylureas), who were given exenatide (10 µg/BID) and who fully completed 4 months, 8 months, and 12 months of follow-ups. RESULTS: Among patients stratified by gender and well matched for age, body mass index, and hemoglobin A1c (HbA1c), it was found that the length of disease was longer in females than in males (12 ± 8 years versus 10 ± 7 years; P = 0.037), and the ratio of patients on metformin to those on combination therapy was higher in men (P = 0.018). Target glycemic response (1-year HbA1c ≤ 7%) was achieved in a significantly higher proportion of males than females (38% versus 27%; χ(2) = 4.66; P = 0.03). Target weight loss expressed as 1-year weight percent fall from baseline ≥ 75th percentile (8.5%) was significantly higher in females at 8 and 12 months (P < 0.05; for both). One-year glycemic target response was inversely related to baseline HbA1c levels and diabetes duration among males, while metformin therapy (compared to oral combination therapy) was a significant predictor of better glycemic targets among females. Homeostasis model assessment-B, measured in 117 patients, predicted hypoglycemic response only in women (P = 0.009). Target 1-year weight loss was predicted by longer diabetes duration among males and by lower baseline HbA1c among females. Finally, no significant difference between genders was noted as to gastrointestinal side effects after exenatide therapy. CONCLUSION: According to this "real world" experience, predictors of glycemic control and body weight loss after 12 months of exenatide BID therapy are different between genders in type 2 diabetes.

1-Hour OGTT Plasma Glucose as a Marker of Progressive Deterioration of Insulin Secretion and Action in Pregnant Women.

Considering old GDM diagnostic criteria, alterations in insulin secretion and action are present in women with GDM as well as in women with one abnormal value (OAV) during OGTT. Our aim is to assess if changes in insulin action and secretion during pregnancy are related to 1-hour plasma glucose concentration during OGTT. We evaluated 3 h/100 g OGTT in 4,053 pregnant women, dividing our population on the basis of 20 mg/dL increment of plasma glucose concentration at 1 h OGTT generating 5 groups (<120 mg/dL, n = 661; 120-139 mg/dL, n = 710; 140-159 mg/dL, n = 912; 160-179 mg/dL, n = 885; and ≥180 mg/dL, n = 996). We calculated incremental area under glucose (AUC(gluc)) and insulin curves (AUC(ins)), indexes of insulin secretion (HOMA-B), and insulin sensitivity (HOMA-R), AUC(ins)/AUC(gluc). AUC(gluc) and AUC(ins) progressively increased according to 1-hour plasma glucose concentrations (both P < 0.0001 for trend). HOMA-B progressively declined (P < 0.001), and HOMA-R progressively increased across the five groups. AUC(ins)/AUC(gluc) decreased in a linear manner across the 5 groups (P < 0.001). Analysing the groups with 1-hour value <180 mg/dL, defects in insulin secretion (HOMA-B: -29.7%) and sensitivity (HOMA-R: +15%) indexes were still apparent (all P < 0.001). Progressive increase in 1-hour OGTT is associated with deterioration of glucose tolerance and alterations in indexes of insulin action and secretion.

Taurine transporter gene expression in peripheral mononuclear blood cells of type 2 diabetic patients.

Taurine acts as antioxidant, cell osmolyte, modulator of glucose metabolism, and plays a role in the retinal function. It is 10(3)-fold more concentrated in the intracellular than in the extracellular milieu due to a specific taurine-Na-dependent transporter (TauT), which is upregulated by hypertonicity, low extracellular taurine, or oxidative stress and acutely downregulated 'in vitro' by high glucose concentrations. Aim of this study was to investigate whether TauT expression was modified in mononuclear peripheral blood cells (MPC) of type 2 diabetic patients with or without micro/macrovascular complications. Plasma taurine, as well as other sulphur-containing aminoacids (assayed by HPLC) and TauT gene expression (assayed by real-time PCR analysis) were measured in MPC of 45 controls and of 81 age-and-sex matched type 2 diabetic patients with or without micro/macrovascular complications. Median value (interquartile range) of plasma taurine was significantly lower in diabetic patients than in controls [28.7 (13.7) µmol/l vs. 46.5 (20.3) µmol/l; P<0.05], while median TauT expression, in arbitrary units, was significantly higher in diabetics than in controls [3.8 (3.9) vs. 1 (1.3); P<0.05) and was related to HbA1c only in controls (r=0.34; P<0.05). Patients with retinopathy (n=25) had lower TauT expression than those who were unaffected [3.1 (2.8) vs. 4.1 (3.4); P<0.05], while persistent micro/macroalbuminuria was associated with unchanged TauT expression. A trend toward reduction in TauT expression was observed in patients with macroangiopathy [n=27; 3.3 (2.5) vs. 4 [3.7]; P=NS]. In conclusion, TauT gene is overexpressed in MPC of type 2 diabetic patients, while presence of retinopathy is specifically associated with a drop in TauT overexpression, suggesting its possible involvement in this microangiopathic lesion.

Gender modulates the relationship between body weight and plasma glucose in overweight or obese subjects.

Obesity and weight increase during adult life are strong predictors of type 2 diabetes. Whether fasting plasma glucose (FPG) is likewise related to body weight as well as with its increase during the adult life in obese-overweight people and whether this relationship is different between the genders is the question asked by the present study. We measured FPG in 1063 overweight-obese subjects (395M/668F) with BMI > or =25 kgm(-2) and classified with no history of diabetes and with a FPG< 7 mmol/l, who consequently came to the Outpatient Clinic of our Diabetes Unit to obtain dietetic advice. Weight increase was determined as the difference between actual weight and weight at 18 years (weight-diff), including only patients with weight-diff> 0. By univariate analysis age, BMI, waist circumference and weight change were loosely related to FPG in both sexes, even if the relation between plasma glucose and anthropometric variables was more consistent in females. By multivariate regression analysis, after adjusting for age, waist circumference, menopausal status and smoking habit, FPG was significantly related to both waist circumference and weight-diff only in women. Odds Ratio for fasting hyperglycaemia (FPG> 6.11 mmol/l), for each S.D. unit increase in weight-diff, after adjusting for age, waist circumference, smoking habit and menopausal status was 1.272; 95% CI: 0.863-1.901 (p=ns) for males and 1.800; 95% CI: 1.239-2.652 (p=0.002) for women. In conclusion our findings suggest that in non-diabetic overweight-obese people, after controlling for main cofounders, anthropometric variables and in particular waist circumference and weight change after 18 years are linearly related to FPG in women, independently predicting the risk of fasting hyperglycaemia only in these latter.

Normal glucose tolerance and gestational diabetes mellitus: what is in between?

OBJECTIVE: The aim of this article was to define the metabolic phenotype of pregnant women with one abnormal value (OAV) during an oral glucose tolerance test (OGTT) and to test whether OAV could be considered metabolically comparable to gestational diabetes mellitus (GDM) or a specific entity between GDM and normal pregnancy. RESEARCH DESIGN AND METHODS: After 100-g 3-h OGTTs, 4,053 pregnant women were classified as having GDM, OAV, or normal glucose tolerance (NGT). Those with OAV were subdivided into three subgroups: fasting hyperglycemia (one abnormal value at fasting during an OGTT), 1-h hyperglycemia (one abnormal value at 1 h during an OGTT [1h-OAV]), or 2- or 3-h hyperglycemia (one abnormal value at 2 or 3 h during an OGTT). As derived from the OGTT, we measured insulin sensitivity (insulin sensitivity index [ISI] Matsuda) and insulin secretion (homeostasis model assessment for the estimation of beta-cell secretion [HOMA-B], first- and second-phase insulin secretion). The product of the first-phase index and the ISI was calculated to obtain the insulin secretion-sensitivity index (ISSI). RESULTS: GDM was diagnosed in 17.9% and OAV in 18.7% of pregnant women; women with GDM and OAV were older and had higher BMI and serum triglyceride levels than those with NGT (all P < 0.05). Women with NGT had the highest ISI followed by those with OAV (-21.7%) and GDM (-32.1%). HOMA-B results were comparable with those for OAV and GDM but significantly (P < 0.01) lower than those for NGT; first- and second-phase insulin secretion appeared progressively reduced from that in women with NGT to that in women with OAV and GDM (P < 0.01). ISSI was higher in women with NGT than in women with either OAV (-34%) or GDM (-51.7%) (P < 0.001). Among OAV subgroups, the 1h-OAV subgroup showed the lowest ISSI (P < 0.05). CONCLUSIONS: OAV and GDM are clinically indistinguishable, and both groups are different from women with NGT. Women with GDM and OAV showed impaired insulin secretion and insulin sensitivity, although these defects are more pronounced in women with GDM. Compared with other OAV subgroups, 1h-OAV could be considered a more severe condition.

Improvement of diabetic foot care after the Implementation of the International Consensus on the Diabetic Foot (ICDF): results of a 5-year prospective study.

The aim of this prospective study was to evaluate the efficacy of the implementation of the International Consensus on the Diabetic Foot (ICDF) in the area of Pistoia (Tuscany, Italy), in terms of percentage of population screened, reduction of hospitalization, and reduction of lower extremity amputations. The study was carried out over a 5-year period (1999-2003) in a district general hospital covering a clearly defined and relatively static population. The implementation of ICDF was performed at district health care level, in collaboration with general practitioners, and at the hospital with the establishment of a multidisciplinary care team. The database for this study was extracted from the DRG Tuscany database, and the diabetes foot lesion data source was taken from the Data Elaboration Centre of the Health Care District of Pistoia, cross-checked with the clinical records of the Diabetes Unit. In the period of the study, there was an increase in both the total number of diabetic foot lesions observed and the number of patients with diabetes referred for evaluation to the Diabetes Unit of Pistoia. Following implementation, the total number of hospitalizations for diabetic foot lesions and the duration of clinical stay were reduced. The total incidence of amputations per 100,000 inhabitants decreased from 10.7 in 1999, to 10.1 in 2000, 2.7 in 2001, 6.3 in 2002 and 6.24 in 2003. In particular, while the incidence of major amputations decreased over time, the relative number of minor amputations increased in the first years, stabilizing at a higher rate in later years. Finally, while before 1999 most people from the Pistoia area were referred to various hospitals in Tuscany for diabetic foot problems, during the implementation period almost all were referred to the Diabetic Unit of Pistoia. This study shows the advantages of prospective data collection, demonstrating that the implementation of the International Consensus on the Diabetic Foot can improve foot care in diabetes.

Serum homocysteine levels are increased in women with gestational diabetes mellitus.

Serum homocysteine (sHcy) has been found to be elevated in patients with type 2 diabetes mellitus, as well as in other clinical conditions associated with insulin resistance and/or vascular diseases. The aims of this study were to measure the relationship between sHcy with biohumoral markers of insulin resistance in pregnant women affected with gestational diabetes mellitus (GDM). We studied 2 groups of pregnant women categorized, after a 100-g, 3-hour oral glucose tolerance test (OGTT) as nondiabetic (n = 78) or affected with GDM (n = 15), by measuring sHcy, serum folate, albumin, vitamin B(12), uric acid, and lipids. In both groups, peripheral insulin sensitivity was measured by using the OGTT-derived index of Matsuda and DeFronzo (ISI(OGTT)). Serum homocysteine was significantly higher in the group with GDM compared with nondiabetic women (5.88 +/- 2.26 micromol/L v 4.45 +/- 1.52 micromol/L; P =.003); was inversely related to serum folate (r = -.48; P =.0001), and was significantly related to serum albumin (r =.27; P =.009), 2-hour plasma glucose (r =.25; P =.01), as well as to serum uric acid (r =.23; P =.03). No relationship was observed between sHcy and serum vitamin B(12), serum triglycerides, total, or high-density lipoprotein (HDL) cholesterol, mean blood pressure and ISI(OGTT). Vitamin B(12) was correlated with ISI(OGTT) (r =.36; P =.0005) and inversely with mean blood pressure (r = -.24; P =.02). GDM remained significantly associated with higher sHcy concentrations also after adjusting for age, serum folate, albumin, uric acid, ISI(OGTT), and vitamin B(12) (P =.006). In conclusion, we found that sHcy is significantly increased in women with GDM, independently of other confounding variables, is significantly related to 2-hour OGTT plasma glucose, and seems unrelated to insulin resistance in these subjects.