Serum metabolomics profile of type 2 diabetes mellitus in a Brazilian rural population

Introduction

The development of common forms of diabetes comes from the interaction between environmental and genetic factors, and the consequences of poor glycemic control in these patients could result in several complications. Metabolomic studies for type 2 diabetes mellitus in serum/plasma have reported changes in numerous metabolites, which might be considered possible targets for future mechanistic research. However, the specific role of a particular metabolite as cause or consequence of diabetes derangements is difficult to establish.

Objectives

As type 2 diabetes is a disease that changes the metabolic profile in several levels, this work aimed to compare the metabolomic profiles of type 2 diabetes mellitus and non-diabetic participants. In addition, we exploited our family-based study design to bring a better understanding of the causal relationship of identified metabolites and diabetes.

Methods

In the current study, population based metabolomics was applied in 939 subjects from the Baependi Heart Study. Participants were separated into two groups: diabetic (77 individuals) and non-diabetic (862 individuals), and the metabolic profile was performed by GC/MS technique.

Results

We have identified differentially concentrated metabolites in serum of diabetic and non-diabetic individuals. We identified 72 metabolites up-regulated in type 2 diabetes mellitus compared to non-diabetics. It was possible to recapitulate the main pathways that the literature shows as changed in diabetes. Also, based on metabolomic profile, we separated pre-diabetic individuals (with glucose concentration between 100–125 mg/dL) from non-diabetics and diabetics. Finally, using heritability analysis, we were able to suggest metabolites in which altered levels may precede diabetic development.

Conclusion

Our data can be used to derive a better understanding of the causal relationship of the observed associations and help to prioritize diabetes-associated metabolites for further work.

     

Platelet activity and hypercoagulation in type 2 diabetes

Background

A strong correlation exists between type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), with CVD and the presence of atherosclerosis being the prevailing cause of morbidity and mortality in diabetic populations. T2DM is accompanied by various coagulopathies, including anomalous clot formation or amyloid fibrin(ogen), the presence of dysregulated inflammatory molecules. Platelets are intimately involved in thrombus formation and particularly vulnerable to inflammatory cytokines.

Methods

The aim of this current study was therefore to assess whole blood (hyper)coagulability, platelet ultrastructure and receptor expression, as well as the levels of IL-1β, IL-6, IL-8 and sP-selectin in healthy and diabetic individuals. Platelet morphology was assessed through scanning electron microscopy (SEM), while assessment of GPIIb/IIIa receptor expression was performed with confocal microscopy and flow cytometry with the addition of FITC-PAC-1 and CD41-PE antibodies. IL-1β, IL-6 and IL-8 and sP-selectin levels were assessed using a multiplex assay.

Results

In T2DM there is significant upregulation of circulating inflammatory markers, hypercoagulation and platelet activation, with increased GPIIb/IIIa receptor expression, as seen with flow cytometry and confocal microscopy. Analyses showed that these receptors were additionally shed onto microparticles, which was confirmed with SEM.

Conclusions

Cumulatively, this provides mechanistic evidence that pathological states of platelets together with amyloid fibrin(ogen) in T2DM, might underpin an increased risk for cardiovascular events.

     

Leptin and resistin induce increased procoagulability in diabetes mellitus

Background

Patients with diabetes mellitus (DM) suffer from an increased risk of cardiovascular events caused by thrombotic conditions. Adipose tissue might play a crucial role in this pathogenesis by synthesis of procoagulant mediators. This study was performed to elucidate the role of the adipocytokines leptin and resistin in the development of hypercoagulability and hypofibrinolysis under diabetic conditions.

Methods

Sixty two patients with or without DM were included in our study to measure leptin, resistin and tissue factor (TF) plasma concentrations. Moreover, flow chamber experiments were performed to assess factor Xa and plasmin activity on the surface of HUVECs. Western blot and real-time PCR were performed to determine mRNA and protein expression of main factors of the coagulation and fibrinolytic system.

Results

Patients with diabetes showed increased levels of leptin and resistin (leptin: 25.69 ± 13.9 vs. 15.98 ± 17.5 ng/mL, p < 0.05; resistin: 2.61 ± 0.6 vs. 1.19 ± 0.7 ng/mL, p < 0.05), which were positively correlated with TF. In vitro, leptin and resistin induced increased factor Xa activity (leptin: 4.29 ± 0.57-fold, p < 0.05; resistin 4.19 ± 0.7-fold, p < 0.05 vs. control) on HUVECs as also reflected by elevated TF mRNA and protein expression. Moreover, stimulatory (plasminogen activator inhibitor 1) and inhibitory (tissue plasminogen activator) mediators of the fibrinolytic cascade were induced by leptin and resistin, leading to a balanced plasmin activity regulation.

Conclusions

Leptin and resistin lead to a procoagulant state in HUVECs by inducing TF expression. This mechanism might be one explanation for the prothrombotic state observed under diabetic conditions.     

Association of common variation in the <Emphasis Type="Italic">PPARA</Emphasis>gene with incident myocardial infarction in individuals with type 2 diabetes: A Go-DARTS study

Background

Common variants of the PPARA gene have been found to associate with ischaemic heart disease in non diabetic men. The L162V variant was found to be protective while the C2528G variant increased risk. L162V has also been associated with altered lipid measures. We therefore sought to determine the effect of PPARA gene variation on susceptibility to myocardial infarction in patients with type 2 diabetes. 1810 subjects with type 2 diabetes from the prospective Go-DARTS study were genotyped for the L162V and C2528G variants in the PPARA gene and the association of the variants with incident non-fatal myocardial infarction was examined. Cox's proportional hazards was used to interrogate time to event from recruitment, and linear regression for analysing association of genotype with quantitative clinical traits.

Results

The V162 allele was associated with decreased risk of non-fatal myocardial infarction (HR = 0.31, 95%CI 0.10–0.93 p = 0.037) whereas the C2528 allele was associated with increased risk (HR = 2.77 95%CI 1.34–5.75 p = 0.006). Similarly V162 was associated with a later mean age of diagnosis with type 2 diabetes and C2582 an earlier age of diagnosis. C2528 was also associated with increased total cholesterol and LDL cholesterol, which did not account for the observed increased risk. Haplotype analysis demonstrated that when both rare variants occurred on the same haplotype the effect of each was abrogated.

Conclusion

Genetic variation at the PPARA locus is important in determining cardiovascular risk in both male and female patients with diabetes. This genotype associated risk appears to be independent of the effect of these genotypes on lipid profiles and age of diagnosis with diabetes.

     

Adiponectin,biomarkers of inflammation and changes in cardiac autonomic function: Whitehall II study

Background

Biomarkers of inflammation and adiponectin are associated with cardiovascular autonomic neuropathy (CAN) in cross-sectional studies, but prospective data are scarce. This study aimed to assess the associations of biomarkers of subclinical inflammation and adiponectin with subsequent changes in heart rate (HR) and heart rate variability (HRV) in non-diabetic and diabetic individuals.

Methods

Data are based on up to 25,050 person-examinations for 8469 study participants of the Whitehall II cohort study. Measures of CAN included HR and several HRV indices. Associations between baseline serum levels of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, IL-1 receptor antagonist (IL-1Ra) and adiponectin and 5-year changes in HR and six HRV indices were estimated using mixed-effects models adjusting for age, sex, ethnicity, body mass index (BMI), metabolic covariates and medication. A modifying effect of diabetes was tested.

Results

Higher levels of IL-1Ra were associated with higher increases in HR. Additional associations with measures of HRV were observed for hsCRP, IL-6 and IL-1Ra, but these associations were explained by BMI and other confounders. Associations between adiponectin, HR and HRV differed depending on diabetes status. Higher adiponectin levels were associated with more pronounced decreases in HR and increases in three measures of HRV reflecting both sympathetic and vagal activity, but these findings were limited to individuals with type 2 diabetes.

Conclusions

Higher IL-1Ra levels appeared as novel risk marker for increases in HR. Higher adiponectin levels were associated with a more favourable development of cardiovascular autonomic function in individuals with type 2 diabetes independently of multiple confounders.

     

Risk of development of diabetes mellitus after diagnosis of gestational diabetes

Background

It is generally appreciated that gestational diabetes is a risk factor for type 2 diabetes. However, the precise relation between these 2 conditions remains unknown. We sought to determine the incidence of diabetes mellitus after diagnosis of gestational diabetes.

Methods

We used a population-based database to identify all deliveries in the province of Ontario over the 7-year period from Apr. 1, 1995, to Mar. 31, 2002. We linked these births to mothers who had been given a diagnosis of gestational diabetes through another administrative database that records people with diabetes on the basis of either physician service claims or hospital admission records. We examined database records for these women from the time of delivery until Mar. 31, 2004, a total of 9 years. We determined the presence of diabetes mellitus according to a validated administrative database definition for this condition.

Results

We identified 659 164 pregnant women who had no pre-existing diabetes. Of these, 21 823 women (3.3%) had a diagnosis of gestational diabetes. The incidence of gestational diabetes rose significantly over the 9-year study period, from 3.2% in 1995 to 3.6% in 2001 (p < 0.001). The probability of diabetes developing after gestational diabetes was 3.7% at 9 months after delivery and 18.9% at 9 years after delivery. After adjustment for age, urban or rural residence, neighbourhood income quintile, whether the woman had a previous pregnancy, whether the woman had hypertension after the index delivery, and primary care level before the index delivery, the most significant risk factor for diabetes was having had gestational diabetes during the index pregnancy (hazard ratio 37.28, 95% confidence interval 34.99–40.88; p < 0.001). Age, urban residence and lower income were also important factors. When analyzed by year of delivery, the rate of development of diabetes was higher among the latest subcohort of women with gestational diabetes (delivery during 1999–2001) than among the earliest subcohort (delivery during 1995 or 1996) (16% by 4.7 years after delivery v. 16% by 9.0 years).

Interpretation

In this large population-based study, the rate of development of diabetes after gestational diabetes increased over time and was almost 20% by 9 years. This estimate should be used by clinicians to assist in their counselling of pregnant women and by policy-makers to target these women for screening and preventionRecently, the US Centers for Disease Control and Prevention predicted a 3-fold rise in the prevalence of diabetes mellitus in the United States between 2005 and 2050, from 16.2 million to 48.3 million.¹ Although evidence to support population-based screening as an approach to stem this epidemic is lacking, targeted screening of high-risk populations has been advocated.^2–5 One group at very high risk for diabetes consists of women with a history of gestational diabetes.During pregnancy, women with gestational diabetes display metabolic abnormalities similar to those of people with type 2 diabetes mellitus, such as insulin resistance and reduced β-cell compensation for that resistance.⁶ After delivery, most of these women return to a euglycemic state, but they are at increased risk for overt type 2 diabetes in the future. The rates of development of type 2 diabetes among women with previous gestational diabetes quoted in the literature have been extremely variable, between 3% and 70%.^7–11 Aside from genetic differences among populations, this large variation in the subsequent development of type 2 diabetes may also be due to the use of diverse tests for glucose tolerance in pregnancy, selection bias and, in particular, duration of follow-up.⁹In light of a growing body of evidence that it is possible to delay the development of diabetes among those at high risk,^12–16 it is important to determine the true risk of type 2 diabetes by means of a population-based study; this will allow accurate assessment of the cost-effectiveness and appropriateness of postpartum case management and screening. We sought to determine the incidence of diabetes mellitus in the years following a diagnosis of gestational diabetes.     

Substantial fibrin amyloidogenesis in type 2 diabetes assessed using amyloid-selective fluorescent stains

Background

We have previously shown that many chronic, inflammatory diseases are accompanied, and possibly partly caused or exacerbated, by various coagulopathies, manifested as anomalous clots in the form of ‘dense matted deposits’. More recently, we have shown that these clots can be amyloid in nature, and that the plasma of healthy controls can be induced to form such clots by the addition of tiny amounts of bacterial lipopolysaccharide or lipoteichoic acid. Type 2 diabetes (T2D) is also accompanied by raised levels of LPS.

Methods

We use superresolution and confocal microscopies to investigate the amyloid nature of clots from healthy and T2D individuals.

Results

We show here, with the established stain thioflavin T and the novel stains Amytracker? 480 and 680, that the clotting of plasma from type 2 diabetics is also amyloid in nature, and that this may be prevented by the addition of suitable concentrations of LPS-binding protein.

Conclusion

This implies strongly that there is indeed a microbial component to the development of type 2 diabetes, and suggests that LBP might be used as treatment for it and its sequelae.

     

A preliminary analysis of hepatitis C virus in pancreatic islet cells

Background

An association between hepatitis C virus (HCV) and type 2 diabetes (T2D) is supported by numerous epidemiologic studies. We hypothesized that HCV could infect human pancreatic islet cells in vitro.

Methods

Measures of HCV RNA synthesis and protein production were used to evaluate HCV infection of pancreatic islets recovered from human donors.

Results

Significant co-staining of insulin and the HCV entry factor CD81 was observed in pancreatic islets. Positive- and negative-sense HCV RNA were detected in HCV-exposed islets at days 1, 3, 7, and 14 post-infection. The HCV core and NS3 proteins were expressed and increased with time providing further evidence of viral replication. Interferon and an HCV polymerase inhibitor reduced viral replication in islet cells. In HCV-infected islets, TNFα levels were elevated at days 1, 3, and 7 post-infection, while IL-6 levels were elevated at day 1 but not days 3 or 7. Overall, the expression of miR-122 was low in islets compared to the Huh7.5 hepatocyte-derived cell line, although the relative expression of miR-122 increased in islet cells after viral infection (1, 6.63, and 5.83 at days 1, 3, and 7, respectively).

Conclusions

In this pilot study, viral infection was demonstrated in pancreatic islet cells from multiple donors using complementary measures of viral replication, thus providing evidence of in vitro infection. Altered cytokine expression may contribute to the development of insulin deficiency, and understanding the etiology of diabetes in individuals with HCV infection may facilitate the development of novel treatment modalities and prevention strategies. This in vitro system provides an important model for mechanistic studies of HCV-pancreas interactions and facilitates future studies of the potential impact of viral infection on islet cell function.

     

Small ubiquitin-like modifier 4 M55V polymorphism is not associated with diabetic nephropathy in Iranian type 2 diabetes patients

INTRODUCTION:

We studied the impact of small ubiquitin-like modifier 4 (SUMO4) M55V polymorphism on susceptibility to diabetic nephropathy in Iranian type 2 diabetes patients.

MATERIALS AND METHODS:

The patient group consisted of 50 Iranian type 2 diabetes patients with nephropathy, and the control group consisted of 50 Iranian type 2 diabetes patients without nephropathy. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism method for the M55V.

RESULTS:

The frequency of SUMO4 AA, AG, and GG genotypes were 23%, 18%, and 9% in the patient group and 10%, 22%, and 18% in the control group. There was no significant difference in frequency of SUMO4 genotypes in patients compared to controls.

CONCLUSION:

These findings indicate that SUMO4 M55V polymorphism is not associated with diabetic nephropathy in Iranian type 2 diabetes patients.     

Epidemiology of diabetes mellitus among First Nations and non-First Nations adults

Background

First Nations people in Canada experience a disproportionate burden of type 2 diabetes mellitus. To increase our understanding of this evolving epidemic, we compared the epidemiology of diabetes between First Nations and non-First Nations adults in Saskatchewan from 1980 to 2005.

Methods

We used administrative databases to perform a population-based study of diabetes frequency, incidence and prevalence in adults by ethnic background, year, age and sex.

Results

We identified 8275 First Nations and 82 306 non-First Nations people with diabetes from 1980 to 2005. Overall, the incidence and prevalence of diabetes were more than 4 times higher among First Nations women than among non-First Nations women and more than 2.5 times higher among First Nations men than among non-First Nations men. The number of incident cases of diabetes was highest among First Nations people aged 40–49 , while the number among non-First Nations people was greatest in those aged 70 or more years. The prevalence of diabetes increased over the study period from 9.5% to 20.3% among First Nations women and from 4.9% to 16.0% among First Nations men. Among non-First Nations people, the prevalence increased from 2.0% to 5.5% among women and from 2.0% to 6.2% among men. By 2005, almost 50% of First Nations women and more than 40% of First Nations men aged 60 or older had diabetes, compared with less than 25% of non-First Nations men and less than 20% of non-First Nations women aged 80 or older.

Interpretation

First Nations adults are experiencing a diabetes epidemic that disproportionately affects women during their reproductive years. This ethnicity-based pattern suggests diverse underlying mechanisms that may include differences in the diabetogenic impact of gestational diabetes.The global epidemic of type 2 diabetes mellitus disproportionately affects indigenous and developing populations.¹ Although genotypic variants related to energy balance may underlie this epidemic,² the rapid emergence of type 2 diabetes in genetically diverse populations worldwide is most likely caused by environmental factors. Increasing rates of type 2 diabetes among Canada’s First Nations people, for example, parallel an epidemic of overweight and obesity that has coincided with socio-cultural disruption and a loss of traditional lifestyles.³In Saskatchewan in 1937, diabetes was not detected among the 1500 First Nations people who underwent a tuberculosis survey.⁴ By 1990, almost 10% of the province’s First Nations adults had diabetes;⁵ by 2006, the proportion was over 20%,⁶ while it remained at about 6% in the general population.^5,6 Although an increased prevalence of diabetes among First Nations people has also been documented in other Canadian provinces,³ only recently have consistent diabetes case definitions applied to health care system administrative databases been used to compare differences between large populations of First Nations and non-First Nations people.^7–9We sought to describe the epidemiology of diabetes in Saskatchewan from 1980 to 2005. We reasoned that finding ethnicity-based differences in trends and patterns of type 2 diabetes over the longest period reported for a Canadian jurisdiction would help to clarify the underlying mechanisms behind known disparities and translate into more effective diabetes prevention and management initiatives.     

Development and psychometric testing of a theory-based tool to measure self-care in diabetes patients: the Self-Care of Diabetes Inventory

Background

Self-care is essential for patients with diabetes mellitus. Both clinicians and researchers must be able to assess the quality of that self-care. Available tools have various limitations and none are theoretically based. The aims of this study were to develop and to test the psychometric properties of a new instrument based on the middle range-theory of self-care of chronic illness: the Self-Care of Diabetes Inventory (SCODI).

Methods

Forty SCODI items (5 point Likert type scale) were developed based on clinical recommendations and grouped into 4 dimensions: self-care maintenance, self-care monitoring, self-care management and self-care confidence based on the theory. Content validity was assessed by a multidisciplinary panel of experts. A multi-centre cross-sectional study was conducted in a consecutive sample of 200 type 1 and type 2 diabetes patients. Dimensionality was evaluated by exploratory factor analyses. Multidimensional model based reliability was estimated for each scale. Multiple regression models estimating associations between SCODI scores and glycated haemoglobin (HbA1c), body mass index, and diabetes complications, were used for construct validity.

Results

Content validity ratio was 100%. A multidimensional structure emerged for the 4 scales. Multidimensional model-based reliabilities were between 0.81 (maintenance) and 0.89 (confidence). Significant associations were found between self-care maintenance and HbA1c (p?=?0.02) and between self-care monitoring and diabetes complications (p?=?0.04). Self-care management was associated with BMI (p?=?0.004) and diabetes complications (p?=?0.03). Self-care confidence was a significant predictor of self-care maintenance, monitoring and management (all p?<?0.0001).

Conclusion

The SCODI is a valid and reliable theoretically-grounded tool to measure self-care in type 1 and type 2 DM patients.

     

Increased circulating RANTES in type 2 diabetes

Aim

The pro-atherogenic role of RANTES, a chemokine expressing pleiotropic activities, in the course of type 2 diabetes-related atherosclerosis has been well documented. However, it is not known which of the diabetes-related factors primarily influence serum RANTES levels in patients with type 2 diabetes. Our aim was to investigate relationships between several factors known to be related to an increased risk of atherosclerosis and serum RANTES levels in type 2 diabetic patients.

Methods

A total of 168 subjects were examined, which included 138 patients with type 2 diabetes and 30 non-diabetic controls. Measurements of venous, fasting, plasma glucose, HbA₁c, lipid profile, 1,5-anhydro-D-glucitol (1,5-AG) plasma levels, homocysteine and the fasting, serum C-peptide levels were performed. Serum concentrations of RANTES were assayed using BD? Cytometric Bead Array tests. Peripheral insulin resistance was expressed according to a new index defined by Ohkura et al.

Results

RANTES levels in type 2 diabetic patients correlated with 1,5-AG, fasting glycaemia, HbA₁c and the Ohkura index. Multivariate regression analysis was performed taking into consideration several factors related to the inflammatory process and atherosclerosis, namely the patient’s age, diabetes duration, waist circumference, 1,5-AG, HbA₁c, lipid profile parameters, serum homocysteine levels and Ohkura index, as independent variables potentially influencing serum RANTES levels in type 2 diabetic patients. It is shown that RANTES concentrations in the serum is primarily dependent upon 1,5-AG plasma levels.

Conclusion

Our results suggest that increased serum levels of RANTES in type 2 diabetic patients are closely related to postprandial (acute) hyperglycaemia.

     

Plasma bicarbonate and risk of type 2 diabetes mellitus

Background:

Several biomarkers of metabolic acidosis, including lower plasma bicarbonate and higher anion gap, have been associated with greater insulin resistance in cross-sectional studies. We sought to examine whether lower plasma bicarbonate is associated with the development of type 2 diabetes mellitus in a prospective study.

Methods:

We conducted a prospective, nested case–control study within the Nurses’ Health Study. Plasma bicarbonate was measured in 630 women who did not have type 2 diabetes mellitus at the time of blood draw in 1989–1990 but developed type 2 diabetes mellitus during 10 years of follow-up. Controls were matched according to age, ethnic background, fasting status and date of blood draw. We used logistic regression to calculate odds ratios (ORs) for diabetes by category of baseline plasma bicarbonate.

Results:

After adjustment for matching factors, body mass index, plasma creatinine level and history of hypertension, women with plasma bicarbonate above the median level had lower odds of diabetes (OR 0.76, 95% confidence interval [CI] 0.60–0.96) compared with women below the median level. Those in the second (OR 0.92, 95% CI 0.67–1.25), third (OR 0.70, 95% CI 0.51–0.97) and fourth (OR 0.75, 95% CI 0.54–1.05) quartiles of plasma bicarbonate had lower odds of diabetes compared with those in the lowest quartile (p for trend = 0.04). Further adjustment for C-reactive protein did not alter these findings.

Interpretation:

Higher plasma bicarbonate levels were associated with lower odds of incident type 2 diabetes mellitus among women in the Nurses’ Health Study. Further studies are needed to confirm this finding in different populations and to elucidate the mechanism for this relation.Resistance to insulin is central to the pathogenesis of type 2 diabetes mellitus.¹ Several mechanisms may lead to insulin resistance and thereby contribute to the development of type 2 diabetes mellitus, including altered fatty acid metabolism, mitochondrial dysfunction and systemic inflammation.² Metabolic acidosis may also contribute to insulin resistance. Human studies using the euglycemic and hyperglycemic clamp techniques have shown that mild metabolic acidosis induced by the administration of ammonium chloride results in reduced tissue insulin sensitivity.³ Subsequent studies in rat models have suggested that metabolic acidosis decreases the binding of insulin to its receptors.^4,5 Finally, metabolic acidosis may also increase cortisol production,⁶ which in turn is implicated in the development of insulin resistance.⁷Recent epidemiologic studies have shown an association between clinical markers of metabolic acidosis and greater insulin resistance or prevalence of type 2 diabetes mellitus. In the National Health and Nutrition Examination Survey, both lower serum bicarbonate and higher anion gap (even within ranges considered normal) were associated with increased insulin resistance among adults without diabetes.⁸ In addition, higher levels of serum lactate, a small component of the anion gap, were associated with higher odds of prevalent type 2 diabetes mellitus in the Atherosclerosis Risk in Communities study⁹ and with higher odds of incident type 2 diabetes mellitus in a retrospective cohort study of the risk factors for diabetes in Swedish men.¹⁰ Other biomarkers associated with metabolic acidosis, including higher levels of serum ketones,¹¹ lower urinary citrate excretion¹² and low urine pH,¹³ have been associated in cross-sectional studies with either insulin resistance or the prevalence of type 2 diabetes mellitus. However, it is unclear whether these associations are a cause or consequence. We sought to address this question by prospectively examining the association between plasma bicarbonate and subsequent development of type 2 diabetes mellitus in a nested case–control study within the Nurses’ Health Study.     

The reliability and validity for Japanese type 2 diabetes patients of the Japanese version of the acceptance and action diabetes questionnaire

Background

The purpose of this study was to determing which psychological traits of Japanese type 2 diabetes patients would provide reliability and validity to the Japanese version of the Acceptance and Action Diabetes Questionnaire (AADQ-J).

Methods

Various questionnaires were administered to type 2 diabetes patients who were registered on the database of the research service provider; data from a total of 600 patients (mean?±?SD age was 57.50?±?9.87 years, female 21.83%) were analyzed.

Results

Three items were excluded because of psychometric concerns related to the original 11-item AADQ. Confirmation factor analyses revealed that the eight-item version demonstrated the best indicators of a goodness of fit. The questionnaire showed adequate internal consistency. The questionnaire demonstrated high measurement accuracy in broad trait values by the test information function of Item Response Theory. The questionnaire showed stronger positive correlations with self-care activities and HbA1c than with diabetes distress and depressive mood.

Conclusions

The eight-item Japanese version of AADQ has reliability and validity for type 2 diabetes patients.

     

Newly diagnosed diabetes mellitus as a risk factor for serious liver disease

Background

The negative impact of diabetes mellitus is well recognized, yet little is known about the effect of this disease on the liver, an organ susceptible to nonalcoholic fatty liver disease related to insulin resistance. We evaluated whether adults with newly diagnosed diabetes were at increased risk of serious liver disease.

Methods

We used administrative health databases for the province of Ontario (1994–2006) to perform a population-based matched retrospective cohort study. The exposed group comprised 438 069 adults with newly diagnosed diabetes. The unexposed comparison group — those without known diabetes — consisted of 2 059 708 individuals, matched 5:1 to exposed persons, by birth year, sex and local health region. We excluded individuals with pre-existing liver or alcohol-related disease. The primary study outcome was the subsequent development of serious liver disease, namely, liver cirrhosis, liver failure and its sequelae, or receipt of a liver transplant.

Results

The incidence rate of serious liver disease was 8.19 per 10 000 person-years among those with newly diagnosed diabetes and 4.17 per 10 000 person-years among those without diabetes. The unadjusted hazard ratio was 1.92 (95% confidence interval [CI] 1.83–2.01). After adjustment for age, income, urban residence, health care utilization and pre-existing hypertension, dyslipidemia, obesity and cardiovascular disease, the hazard ratio was 1.77 (95% CI 1.68–1.86).

Interpretation

Adults with newly diagnosed diabetes appeared to be at higher risk of advanced liver disease, also known as diabetic hepatopathy. Whether this reflects nonalcoholic fatty liver disease or direct glycemic injury of the liver remains to be determined.Parallel to adult obesity,¹ the prevalence of type 2 diabetes mellitus has risen to an unprecedented level over the past decade.² The negative impact of diabetes on the retinal, renal, nervous and cardiovascular systems is well recognized,^3,4 yet little is known about its effect on the liver. It has recently been realized that hepatic dysregulation in the setting of obesity is marked by oxidative stress and steatosis related to insulin resistance.⁵ The ensuing effect is nonalcoholic fatty liver disease, a common spectrum of disease ranging from simple steatosis (fatty infiltration) to inflammatory steatohepatitis to possible long-term injury (fibrosis and cirrhosis) and eventual liver failure.⁶ Recent evidence has even suggested that elevated levels of aminotransferase may be a marker of future risk of diabetes.⁷Existing guidelines do not advocate screening for liver-related complications among persons with diabetes, making the liver a potentially neglected target organ. Diabetes-associated hepatopathy has been described largely in uncontrolled patient series;⁸ however, those reports did not assess the development of serious liver disease. In one large cohort study based on computerized national databases of the US Department of Veterans Affairs, the incidence of chronic nonalcoholic liver disease was nearly two times higher among those with diabetes.⁹ However, the study sample consisted almost entirely of older men requiring care in hospital, for whom the duration of diabetes was unknown.We conducted a population-based study to evaluate whether adults with newly diagnosed diabetes were at increased risk of serious liver disease relative to matched controls without diabetes.     

Breast size and risk of type 2 diabetes mellitus

Background

Elevated waist circumference and body mass index (BMI), both traditional measures of obesity, are accepted risk factors for type 2 diabetes mellitus. Girls who are obese experience earlier onset of puberty and possibly greater breast development. We sought to evaluate whether a woman''s breast size in late adolescence is associated with an increased risk of type 2 diabetes mellitus in adulthood.

Methods

In conjunction with the ongoing Nurses'' Health Study II, which began to study risk factors for breast cancer among women in 1989, we conducted a prospective cohort study involving 92 106 of the participants. We assessed the risk of type 2 diabetes mellitus in relation to self-reported bra cup sizes, categorized as ≤ A, B, C and ≥ D cups, among participants at age 20.

Results

The mean age of participants at baseline was 38.1 years. A total of 1844 new cases of type 2 diabetes mellitus arose at a mean age of 44.9 years during 886 443 person-years of follow-up. Relative to bra cup size ≤ A, the respective age-adjusted hazard ratios (and 95% confidence intervals [CIs]) were 2.30 (1.99–2.66) for B cup, 4.32 (3.71–5.04) for C cup and 4.99 (4.12–6.05) for ≥ D cup. Upon further adjustments for age at menarche, parity, physical activity, smoking status, diet, multivitamin use, family history of diabetes mellitus, BMI at age 18 and current BMI, the corresponding hazard ratios (and 95% CIs) were 1.37 (1.18–1.59) for B cup, 1.80 (1.53- 2.11) for C cup and 1.64 (1.34–2.01) for ≥ D cup. The addition of waist circumference to this model minimally changed the hazard ratios (and 95% CIs): 1.32 (1.14–1.53) for B cup, 1.71 (1.46–2.01) for C cup and 1.58 (1.29–1.94) for ≥ D cup.

Interpretation

A large bra cup size at age 20 may be a predictor of type 2 diabetes mellitus in middle-aged women. Whether this relation is independent of traditional indicators of obesity remains to be determined.Obesity is an established risk factor for type 2 diabetes mellitus.^1,2 Affected individuals show signs of insulin resistance and hyperinsulinemia, a process that may begin in childhood.^3,4 Pre-adolescent obesity is also an important predictor of age of onset of breast development in young women, and of breast size after puberty.^5,6 Premature onset of puberty is preceded by childhood insulin resistance, hyperinsulinemia and hyperandrogenemia,⁷ which may persist after puberty⁸ and continue into early adulthood.⁹Although an elevated body mass index (BMI)^10,11 and central adiposity¹² are established risk factors for insulin resistance and the onset of type 2 diabetes mellitus, little is known about the contribution of extra-abdominal adipose tissue, including breast tissue, about 60% of which is fatty tissue, to this process.^13,14 We hypothesized that a woman''s breast size in late adolescence reflects her predisposition to insulin resistance and type 2 diabetes mellitus that is both additive to, and independent of, BMI. We explored this hypothesis in conjunction with the Nurses'' Health Study II by relating bra cup size, a proxy for breast size, to the onset of type 2 diabetes mellitus.     

Breastfeeding and its impact on daily life in women with type 1 diabetes during the first six months after childbirth: a prospective cohort study

Background

For mothers with diabetes, breastfeeding is a great challenge due to their struggle with potentially unstable blood glucose levels. This paper explores breastfeeding attitudes and impact of breastfeeding on the daily life of mothers with type 1 diabetes compared with non-diabetic mothers.

Methods

We performed a prospective cohort study of 108 mothers with type 1 diabetes and a reference group of 104 mothers in the west of Sweden. Data were collected through medical records and structured telephone interviews at 2 and 6 months after childbirth.

Results

Women in both the diabetes group and the reference group had high levels of confidence (84% and 93% respectively) in their breastfeeding capacity before childbirth, and 90% assessed breastfeeding as a positive and an important experience during the six months of follow-up. About 80% assessed breastfeeding as influencing daily life ‘very much’ or ‘quite a lot’ at 2 months as did 60% at 6 months, with no difference between the groups. In mothers with diabetes, the impact of breastfeeding on the priority of other duties decreased over time, as did feelings of time pressure and negative effects on patterns of sleep. Compared to the reference group, mothers with diabetes at 6 months remained more affected by disruptions in daily life and they felt more worried about their health both at 2 and 6 months after childbirth. For the reference group mothers’ sensitivity to unexpected disruptions in daily routines decreased between 2 and 6 months after childbirth, and they expressed a greater need to organize their time than mothers with diabetes.

Conclusion

Mothers with diabetes type 1 express more worry for own health and are more sensitive to distruptions. To balance their everyday life and to reduce the risk of stress and illhealth they are therefor, compared to other mothers, likely to need additional professional and peer support.

     

Cardiovascular risk reduction over time in patients with diabetes or pre-diabetes undergoing bariatric surgery: data from a single-center retrospective observational study

Background

Bariatric surgery is effective in remission of obesity comorbidities. This study was aimed at comparing CVD risk between morbidly obese patients with type 2 diabetes and pre-diabetes before and after bariatric surgery as well as assessing comorbidities.

Methods

This is a retrospective observational study with 105 patients with type 2 diabetes (DMbaseline) and prediabetes (preDMbaseline) who underwent Roux-en-Y gastric bypass. Data were collected preoperative and then at 3,6,12,18,24,36,48, and 60?months after surgery. Anthropometric, cardiovascular and glycemic parameters were assessed. CVD risk was calculated using the Framingham Risk Score.

Results

Prior to surgery, 48 patients had type 2 diabetes, while 57 had pre-diabetes. Mean age was 48 (9.2) and mean BMI was 52 (7.4). 26.1% of patients had a high CVD risk. CVD risk decreased in patients with type 2 diabetes and prediabetes at month 12 after surgery compared to the baseline risk (p?<?0.001). BMI, body fat percentage, fasting plasma glucose, HbA1c, c-peptide, HOMA-IR, LDL-c, systolic blood pressure, and diastolic blood pressure decreased during the first year after surgery. From the 12th month until the 60th, they showed a flat trend, or a very mild increase in some cases. 3.2% of patients maintained high CVD risk at 60?months. Type 2 diabetes remission was 92%. No patient of the preDMbaseline group developed type 2 diabetes.

Conclusion

Bariatric surgery reduces CVD risk in type 2 diabetes and pre-diabetes. Given that patients with type 2 diabetes benefit the most, more studies are necessary to consider pre-diabetes as a criterion for metabolic surgery in patients with BMI?≥?35?kg/m².