Urinary biomarkers involved in type 2 diabetes: a review

Diabetes mellitus is one of the most challenging health concerns of the 21st century. With at least 30% of the diabetic population remaining undiagnosed, effective and early diagnosis is of critical concern. Development of a diagnostic test, more convenient and reliable than those currently used, would therefore be highly beneficial. Urine as a diagnostic medium allows for non‐invasive detection of biomarkers, including some associated with type 2 diabetes and its complications. This review provides a synopsis of those urinary biomarkers that potentially may provide a basis for the development of improved diagnostic tests. Three main pathways for the sourcing of potential makers are identified: kidney damage, oxidative stress and low‐grade inflammation including atherosclerosis/vascular damage. This review briefly presents each pathway and some of the most relevant urinary biomarkers that may be used to monitor the development or progression of diabetes and its complications. In particular, biomarkers of renal dysfunction such as transferrin, type IV collagen and N‐acetyl‐β‐D ‐glucosaminidase might prove to be more sensitive than urinary albumin, the current gold standard, in the detection of incipient nephropathy and risk assessment of cardiovascular disease. Inflammatory markers including orosomucoid, tumour necrosis factor‐α, transforming growth factor‐β, vascular endothelial growth factor and monocyte chemoattractant protein‐1, as well as oxidative stress markers such as 8‐hydroxy‐2′deoxyguanosine may also be useful biomarkers for diagnosis or monitoring of diabetic complications, particularly kidney disease. However, the sensitivity of these markers compared with albumin requires further investigation. Copyright © 2010 John Wiley & Sons, Ltd.     

Longitudinal study investigating serum metabolites and their association with type 2 diabetes risk in a Korean population

Aim

The lack of longitudinal metabolomics data and the statistical techniques to analyse them has limited the understanding of the metabolite levels related to type 2 diabetes (T2D) onset. Thus, we carried out logistic regression analysis and simultaneously proposed new approaches based on residuals of multiple logistic regression and geometric angle-based clustering for the analysis in T2D onset-specific metabolic changes.

Materials and methods

We used the sixth, seventh and eighth follow-up data from 2013, 2015 and 2017 among the Korea Association REsource (KARE) cohort data. Semi-targeted metabolite analysis was performed using ultraperformance liquid chromatography/triple quadrupole-mass spectrometry systems.

Results

As the results from the multiple logistic regression and a single metabolite in a logistic regression analysis varied dramatically, we recommend using models that consider potential multicollinearity among metabolites. The residual-based approach particularly identified neurotransmitters or related precursors as T2D onset-specific metabolites. By using geometric angle-based pattern clustering studies, ketone bodies and carnitines are observed as disease-onset specific metabolites and separated from others.

Conclusion

To treat patients with early-stage insulin resistance and dyslipidaemia when metabolic disorders are still reversible, our findings may contribute to a greater understanding of how metabolomics could be used in disease intervention strategies during the early stages of T2D.     

High saturated-fat and low-fibre intake: a comparative analysis of nutrient intake in individuals with and without type 2 diabetes

Objective:

The aim of dietary modification, as a cornerstone of type 2 diabetes (T2DM) management, is to optimise metabolic control and overall health. This study describes food and nutrient intake in a sample of adults with T2DM, and compares this to recommendations, and to intake in age, sex, body mass index (BMI) and social-class matched adults without T2DM.

Design:

A cross-sectional analysis of food and nutrient intake in 124 T2DM individuals (64% male; age 57.4±5.6 years, BMI 32.5±5.8 kg m⁻²) and 124 adults (age 57.4±7.0 years, BMI 31.2±5.0 kg m⁻²) with no diabetes (ND) was undertaken using a 4-day semiweighed food diary. Biochemical and anthropometric variables were also measured.

Results:

While reported energy intake was similar in T2DM vs ND (1954 vs 2004 kcal per day, P=0.99), T2DM subjects consumed more total-fat (38.8% vs 35%, P⩽0.001), monounsaturated-fat (13.3% vs 12.2% P=0.004), polyunsaturated-fat (6.7% vs 5.9% P<0.001) and protein (18.6% vs 17.5%, P⩽0.01). Both groups exceeded saturated-fat recommendations (14.0% vs 13.8%). T2DM intakes of carbohydrate (39.5% vs 42.9%), non-milk sugar (10.4% vs 15.0%) and fibre (14.4 vs 18.9 g) were significantly lower (P<0.001). Dietary glycaemic load (GL) was also lower in T2DM (120.8 vs 129.2; P=0.02), despite a similar glycaemic index (59.7 vs 60.1; P=0.48). T2DM individuals reported consuming significantly more wholemeal/brown/wholegrain breads, eggs, oils, vegetables, meat/meat products, savoury snacks and soups/sauces and less white breads, breakfast cereals, cakes/buns, full-fat dairy, chocolate, fruit juices, oily fish and alcohol than ND controls.

Conclusion:

Adults with T2DM made different food choices to ND adults. This resulted in a high saturated-fat diet, with a higher total-fat, monounsaturated-fat, polyunsaturated-fat and protein content and a lower GL, carbohydrate, fibre and non-milk sugar content. Dietary education should emphasise and reinforce the importance of higher fibre, fruit, vegetable and wholegrain intake and the substitution of monounsaturated for saturated-fat sources, in energy balanced conditions.     

Long-term effects of coffee and caffeine intake on the risk of pre-diabetes and type 2 diabetes: Findings from a population with low coffee consumption

Background and aim

Here, we examined the potential effect of coffee consumption and total caffeine intake on the occurrence of pre-diabetes and T2D, in a population with low coffee consumption.

Coffee consumption, type 2 diabetes and impaired glucose tolerance in Swedish men and women

OBJECTIVES: The association between coffee consumption, type 2 diabetes and impaired glucose tolerance was examined. In addition, indicators of insulin sensitivity and beta-cell function according to homeostasis model assessment were studied in relation to coffee consumption. DESIGN: Population-based cross-sectional study. SETTING AND SUBJECTS: The study comprised 7949 healthy Swedish subjects aged 35-56 years residing within five municipalities of Stockholm. An oral glucose tolerance test identified 55 men and 52 women with previously undiagnosed type 2 diabetes and 172 men and 167 women with impaired glucose tolerance. Information about coffee consumption and other factors was obtained by questionnaire. RESULTS: The relative risks (adjusted for potential confounders) of type 2 diabetes and impaired glucose tolerance when drinking >/=5 cups of coffee per day compared with /=5 cups day(-1)) was inversely associated with insulin resistance. In addition, in those with type 2 diabetes and in women (not in men) with impaired glucose tolerance high coffee consumption was inversely associated with low beta-cell function. In women, but not obviously in men, with normal glucose tolerance, coffee consumption was associated with a reduced risk of insulin resistance. CONCLUSIONS: The results of this study indicated that high consumers of coffee have a reduced risk of type 2 diabetes and impaired glucose tolerance. The beneficial effects may involve both improved insulin sensitivity and enhanced insulin response.     

Metformin‐associated risk of acute dialysis in patients with type 2 diabetes: A nationwide cohort study

Recent guidelines governing anti‐diabetic medications increasingly advocate metformin as first‐line therapy in all patients with type 2 diabetes. However, metformin could be associated with increased risk of acute kidney injury (AKI), acute dialysis and lactate acidosis in marginal patients. In a retrospective nationwide cohort study, a total of 168 443 drug‐naïve patients with type 2 diabetes ≥50 years, initiating treatment with either metformin or sulphonyl in Denmark between 2000 and 2012 were included in this study (70.7% initiated treatment with metformin); calculation of 1‐year risk of acute dialysis was based on g‐standardization of cause‐specific Cox regression models for acute dialysis, end‐stage renal disease and death. One‐year risks of acute dialysis were 92.4 per 100 000 (95% CI, 67.1‐121.3) and 142.7 per 100 000 (95% CI, 118.3‐168.0) for sulphonylurea and metformin, respectively. The metformin‐associated 1‐year risk of acute dialysis was increased by 50.3 per 100 000 (95% CI, 7.9‐88.6), corresponding to a risk ratio of 1.53 (95% CI, 1.06‐2.23), and a number needed to harm of 1988, thus providing evidence of potential concerns pertaining to the increasing use of metformin.     

Cardiovascular biomarkers in clinical studies of type 2 diabetes

When planning cardiovascular (CV) studies in type 2 diabetes (T2D), selection of CV biomarkers is a complex issue. Because the pathophysiology of CV disease (CVD) in T2D is multifactorial, ideally, the selected CV biomarkers should cover all aspects of the known pathophysiology of the disease. This will allow the researcher to distinguish between effects on different aspects of the pathophysiology. To this end, we discuss a host of biomarkers grouped according to their role in the pathogenesis of CVD, namely: (1) cardiac damage biomarkers; (2) inflammatory biomarkers; and (3) novel biomarkers (oxidative stress and endothelial dysfunction biomarkers). Within each category we present the best currently validated biomarkers, with special focus on the population of interest (people with T2D). For each individual biomarker, we discuss the physiological role, validation in the general population and in people with T2D, analytical methodology, modifying factors, effects of glucose‐lowering drugs, and interpretation. This approach will provide clinical researchers with the information necessary for planning, conducting and interpreting results from clinical trials. Furthermore, a systematic approach to selection of CV biomarkers in T2D research will improve the quality of future research.     

家族史与2型糖尿病发病风险关联性的研究进展

2型糖尿病(T2DM)的发病形势日趋严峻,被普遍认为是一种多因素导致的疾病,而糖尿病家族史是T2DM进展过程中的重要独立风险因素之一,可综合反映遗传易感性与共享环境因素对T2DM发病的影响,本文将针对遗传易感性和共享环境因素两方面阐述糖尿病家族史与T2DM发病风险的关联性。     

Non-diabetic relatives of Type 2 diabetic families: dietary intake contributes to the increased risk of diabetes.

AIMS: Non-diabetic first degree relatives of Type 2 diabetic patients are at increased risk of developing diabetes and cardiovascular disease. This is assumed to reflect a shared genetic predisposition. The aim of this study was to test the hypothesis that lifestyle factors, specifically dietary factors, are also important to the increased risk in non-diabetic relatives. METHODS: Dietary intake was assessed using a validated food frequency questionnaire in 149 non-diabetic first degree relatives (age 20-65 years) from families of North European extraction with two or more living Type 2 diabetic family members, and 143 age- and sex-matched control subjects from the background population with no family history of diabetes. RESULTS: Relatives reported higher absolute intakes of total fat (mean (95% confidence intervals) 83 (76-91) vs. 71 (66-76) g/day, P = 0.01), saturated fat (SFA; 39 (36-43) vs. 33 (30-36) g/day, P < 0.01) and cholesterol (391 (354-427) vs. 318 (287-349) mg/day, P < 0.01), and a lower intake of non-starch polysaccharide (P < 0.05). Considered as percentage of total daily energy intake, relatives had higher intakes of total fat (P < 0.01) and SFA (P < 0.02), and a lower intake of carbohydrate (P < 0.02). These differences remained after exclusion of suspected under- and over-reporters of dietary intake. CONCLUSIONS: Non-diabetic relatives of Type 2 diabetic patients were found to consume diets that will promote rather than prevent the development of diabetes and cardiovascular disease. This suggests that the increased risk to non-diabetic relatives is therefore not entirely genetic, and there is scope for decreasing the risk through lifestyle modification.     

Dietary intake in Japanese patients with type 2 diabetes: Analysis from Japan Diabetes Complications Study

Aims/Introduction

Though there are many differences in dietary habits and in the metabolic basis between Western and Asian people, the actual dietary intake in Asian patients with diabetes has not been investigated in a nationwide setting, unlike in Western countries. We aimed to clarify dietary intake among Japanese individuals with type 2 diabetes, and identify differences in dietary intake between Japanese and Western diabetic patients.

Materials and Methods

Nutritional and food intakes were surveyed and analyzed in 1,516 patients with type 2 diabetes aged 40–70 years from outpatient clinics in 59 university and general hospitals using the food frequency questionnaire based on food groups (FFQg).

Results

Mean energy intake for all participants was 1737 ± 412 kcal/day, and mean proportions of total protein, fat, and carbohydrate comprising total energy intake were 15.7, 27.6 and 53.6%, respectively. They consumed a ‘low‐fat energy‐restricted diet’ compared with Western diabetic patients, and the proportion of fat consumption was within the suggested range that has been traditionally recommended in Western countries. As a protein source, consumption of fish (100 g) and soybean products (71 g) was larger than that of meat (50 g) and eggs (29 g). These results imply that dietary content and food patterns among Japanese patients with type 2 diabetes are quite close to those reported as suitable for prevention of obesity, type 2 diabetes, cardiovascular disease, and total mortality in Europe and America.

Conclusions

A large difference was shown between dietary intake by Japanese and Western patients. These differences are important to establish ethnic‐specific medical nutrition therapy for diabetes.     

Patients with type 2 diabetes mellitus have higher risk for acute pancreatitis compared with those without diabetes

Aim: The aetiology of acute pancreatitis (AP) is complex, and many risk factors for AP are shared by patients with type 2 diabetes mellitus (T2DM). However, few have assessed risk factors for AP specifically in T2DM patients. Methods: Patients in the General Practice Research Database (2 984 755, 5.0% with T2DM) were used to estimate incidence of AP for T2DM relative to non‐diabetes, adjusting for prior pancreatitis, gallbladder disease, obesity, smoking and alcohol use. Multivariate Cox regression analysis adjusting for risk factors and Charlson comorbidity index (CCI) was used to estimate hazard ratios (HR) with 95% confidence intervals (CI). Results: Between 2003 and 2007, 301 of 148 903 patients with T2DM and 2434 of almost 3 million patients without diabetes developed AP. Patients with T2DM had higher risk for AP compared with patients without diabetes (crude HR: 2.89, 95% CI: 2.56–3.27). Patients with T2DM had significantly higher rates of prior alcohol and tobacco exposure (44.2 and 61.9% vs. 34.1 and 35.9%, p < 0.001) and of comorbid conditions (14.7% with CCI ≥1 vs. 4.3%, p < 0.001). Histories of obesity, pancreatitis, gallbladder disease, smoking or alcohol use were significant predictors of AP. After adjusting for these factors, age, gender and comorbidities, the risk of developing AP remained elevated in patients with T2DM (adjusted HR: 1.49, 95% CI: 1.31–1.70). Conclusion: After adjusting for risk factors, patients with T2DM had an elevated risk of AP compared with patients without diabetes. Physicians should be aware of the increased risk in patients with T2DM, particularly in those with prior pancreatitis.     

Alcohol intake, consumption pattern and beverage type, and the risk of Type 2 diabetes.

AIMS: To examine associations between amount and frequency of alcohol consumption, and Type 2 diabetes. METHODS: A prospective study of 36 527 adults aged 40-69 at baseline. Incident cases of Type 2 diabetes were identified by questionnaire 4 years later. Sex-specific logistic regression models, adjusting for country of birth, dietary glycaemic index, energy intake and age, and in a second model body mass index (BMI) and waist-hip ratio (WHR), were used. RESULTS: Diabetes status was ascertained for 31 422 (86%) participants, and 362 cases identified. Former drinkers had higher risks than lifetime abstainers. Female drinkers had lower risk than lifetime abstainers (ORs < 10 g/day 0.54, 95% CI 0.36-0.82; 10-19.9 g/day 0.57, 0.34-0.94; > or = 20 g/day 0.46, 0.24-0.88, P trend = 0.005). There was no relationship after adjustment for body size. For men, a weak inverse association was observed after adjustment for body size (ORs relative to lifetime abstainers: < 10 g/day 1.56, 0.95-2.55; 10-19.9 g/day 1.21, 0.69-2.10; 20-29.9 g/day 0.80, 0.40-1.60; = 30 g/day 0.86, 0.50-1.58, P trend = 0.036). Wine was the only beverage for which an inverse association was observed. Compared with men who did not drink in the week before baseline, men who drank > or = 210 g over 1-3 days had an increased risk of diabetes (OR 5.21, 1.79-15.19), while the same amount over more days did not increase risk. CONCLUSIONS: Total alcohol intake was associated with reduced risk only in women. Alcohol from wine was associated with reduced risk of Type 2 diabetes. A high daily intake of alcohol, even on only 1-3 days a week, may increase the risk of diabetes in men.