Is there any relation between diabetes therapy and cancer risk?

Type 2 diabetes is associated with increased risk of cancer. This risk is related to HbA1 increase and this influence is present also in prediabetes and in nondiabetics with HbA1c in upper normal range. In last 2 years, it was concluded that that the specific antidiabetic therapy could influence the cancer risk. In this review we show that reduction of HbA1c does not change cancer risk. Most important is the risk reduction of cancer risk by metformin. Insulin therapy and the use ofsulphonylurea related drugs, increases the risk of cancer. This risk can be eliminated in the combination with metformin. Other published results including the suspected effect related to the use of glargine, pioglitazone, sitagliptine and exenatide are inconsistent and analysis of long term effects of these drugs is necessary. The large discussion in many publications shows the important role of FDA and EMA. This agencies do not suspend drugs without consistent evaluation of results.     

Is there a relationship between left ventricular mass and plasma glucose and lipids independent of body mass index? Results of the Gubbio Study

BACKGROUND AND AIMS: The association between left ventricular (LV) mass (M) and variables described as features of the insulin resistance syndrome, such as obesity and measures o lipid and carbohydrate metabolisms, has been reported in hypertensives. The aim of the present study was to investigate in a large, population based group of non hypertensive people, the prevalence of LV hypertrophy (H) and the relationship of LVM with some of the variables described in the insulin resistance syndrome, independently of obesity. For this reason we investigated the normotensive subjects in the age range 45-54 yrs (n = 435) of the total population of participants in the Gubbio Population Study. METHODS AND RESULTS: Serum lipids, cholesterol (Chol), triglyceride (Tg), HDL cholesterol, fasting blood glucose (FBG), blood pressure (BP), body weight and height were measured and body mass index (BMI) was calculated; LVM was assessed by M-mode echocardiography. Using a normalization criterion not related to body weight (g/m2.7) and the cut-off of 49.2 g/m2.7 for men and 46.7 g/m2.7 for women, LVH was found in 25% of the sample whilst, when LVM was corrected by body surface area (cut-off 116 g/m2 for men and 104 g/m2 for women), the prevalence of LVH was quite lower (10.3%). In the univariate analyses LVMi was closely related to BP, BMI and metabolic variables whilst in the multivariate analysis only BP, BMI, and age were detected as independent predictors of LVMi. When the sample was divided into obese and non-obese subjects on the basis of BMI (cut-off 30 kg/m2), no difference in metabolic variables was seen between subjects with and without LVH within each BMI class. Regarding left ventricular geometry, RWT was positively related to triglycerides and blood glucose and inversely to HDL-chol. CONCLUSIONS: The present study in the middle age normotensive sample of the general population of Gubbio extends to normotensives the relationship between left ventricular mass and metabolic parameters already seen in hypertensives. BMI seems to account for most of the increases in LVM since the prevalence of LVH, which was definitely high when LVM was not normalized to body weight, fell to approximately 4% when the influence of body weight was excluded. Moreover differences in metabolic values between subjects with and without LVH disappeared when the subjects were stratified by BMI. Left ventricular geometry, on the other hand, seems to be related to some metabolic variables.     

Does diabetes mellitus with or without gallstones increase the risk of gallbladder cancer? Results from a population-based cohort study

Background

Previous studies have suggested that diabetes mellitus (DM) is a risk factor for gallbladder cancer; however, it remains unclear whether DM with or without gallstones increases the risk of gallbladder cancer. The aim of this study was to evaluate the risk factors for gallbladder cancer, including sex, hypertension, hyperlipidemia, gallstones, and DM.

Methods

The study cohort consisted of 214,179 subjects newly diagnosed with diabetes (cases) collected from the claims data of the Health Insurance Program of Taiwan from 2000 to 2001 who were retrospectively enrolled. The control group consisted of 206,860 subjects without diabetes, matched with the cases for sex, age, and index year. The subjects were followed up until the end of 2008. The effects of the risk factors on the incidence of gallbladder cancer were evaluated with Cox’s proportional hazard regression models.

Results

The risk of gallbladder cancer was higher in the DM group than in the non-DM group, with a hazard ratio (HR) of 1.53 [95 % confidence interval (CI) 1.22–1.90]. Gallstones were also a risk factor for gallbladder cancer, with an HR of 2.52 (95 % CI 1.11–5.73). DM and gallstones were synergistic risk factors for gallbladder cancer (p < 0.0001), with an HR of 5.37 (95 % CI 3.17–9.10) for subjects with both diseases in relation to those with neither of these conditions.

Conclusions

In the present long-term cohort study, DM with or without gallstones increased the risk of gallbladder cancer. Gallstones were independently related to gallbladder cancer, and DM and gallstones were synergistic risk factors for gallbladder cancer.     

Do breast-feeding and other reproductive factors influence future risk of rheumatoid arthritis? Results from the Nurses' Health Study

OBJECTIVE: To explore the contribution of female hormonal factors occurring prior to the onset of rheumatoid arthritis (RA), such as age at menarche, parity, age at first birth, breast-feeding, use of oral contraceptives (OCs), irregular menstrual cycles, and postmenopausal hormone (PMH) use, to the subsequent development of RA in a large female cohort. METHODS: We studied female reproductive and hormonal risk factors for RA in a cohort of 121,700 women enrolled in the longitudinal Nurses' Health Study. The diagnosis of incident RA (between 1976 and 2002) in 674 women was confirmed by a connective tissue disease screening questionnaire and blinded medical record review for American College of Rheumatology criteria. Sixty percent of the patients with RA were rheumatoid factor positive. The relationship between potential risk factors, including age, age at menarche, parity, age at first birth, total lifetime history of breast-feeding, use of OCs, and irregular menstrual cycles and the multivariate-adjusted risk of RA was estimated using Cox proportional hazards models. RESULTS: Using a multivariate model that adjusted for age, body mass index, smoking, parity, and other hormonal factors, we observed a strong trend for decreasing risk of RA with increasing duration of breast-feeding (P for trend = 0.001). For women who breast-fed (compared with parous women who did not breast-feed), the risk ratios (RRs) and 95% confidence intervals (95% CIs) were as follows: breast-feeding for < or =3 total months, RR 1.0 (95% confidence interval [95% CI] 0.8-1.2); for 4-11 total months, RR 0.9 (95% CI 0.7-1.1); for 12-23 total months, RR 0.8 (95% CI 0.6-1.0); and for > or =24 total months, RR 0.5 (95% CI 0.3-0.8). Very irregular menstrual cycles were associated with an increased risk of RA (RR 1.4, 95% CI 1.0-2.0). Age at menarche < or =10 years was associated with an increased risk of seropositive RA (RR 1.6, 95% CI 1.1-2.4) but not significantly associated with risk of RA. Parity, total number of children, age at first birth, and OC use were not associated with an increased risk of RA in this cohort. CONCLUSION: In this large cohort, breast-feeding for >12 months was inversely related to the development of RA. This apparent effect was dose-dependent, with a significant trend toward lower risk with longer duration of breast-feeding. Irregular menstrual cycles and earlier age at menarche increased the risk of RA. Other reproductive hormonal factors were not associated with RA risk.     

Do the ethanol metabolizing enzymes modify the relationship between alcohol consumption and blood pressure?

BACKGROUND: Several cross-sectional studies have examined whether the relationship between alcohol consumption and blood pressure (alcohol-BP relationship) differs among individuals with different aldehyde dehydrogenase-2 (ALDH2) genotypes, but few studies have examined the association with alcohol dehydrogenase-2 (ADH2), and those have yielded inconsistent results. We examined the potential modulatory effects of ADH2 and ALDH2 genotypes on the alcohol-BP relationship in a cross-sectional sample of a Japanese rural community. METHODS AND RESULTS: The study subjects were 335 randomly selected men aged 40-69 years, who lived in Shiso, a Japanese rural county, in 1999 or 2000. The genetic polymorphisms of ADH2 and ALDH2 were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. The frequencies of ADH21/21 (wild-type), 21/22 (superactive heterozygotes), and 22/22 (superactive homozygotes) were 8.4, 34.9 and 56.7%, respectively; and those of ALDH21/21 (wild-type), 21/22 (inactive heterozygotes), and 22/22 (inactive homozygotes) were 52.8, 40.9, and 6.3%, respectively. A multiple linear regression analysis showed that the relationship between alcohol consumption and diastolic blood pressure was significantly stronger in men with ADH21/21 than those with ADH21/22 or 22/22 (adjusted regression coefficient = 0.0392 versus 0.0113 mmHg for + 1 g ethanol/week, P for difference in slope = 0.018). The strength of the alcohol-BP relationship was similar in all of the ALDH2 genotype groups. CONCLUSION: The alcohol-BP relationship was significantly stronger in men with ADH21/21 than in men with ADH21/22 or 22/22 in this Japanese rural population. This finding was exactly the opposite of what one previous study suggested.     

Is the newly suggested fasting plasma glucose cut-off point for the diagnosis of diabetes the right one?

Letters

Is the newly suggested fasting plasma glucose cut-off point for the diagnosis of diabetes the right one?     

Is there a causal relation between obesity and asthma? Evidence from Chile

OBJECTIVE: An association between obesity and asthma symptoms has been reported in the literature, but such a relationship is inconsistent if atopic status or bronchial hyper responsiveness (BHR) is considered. The objective was to assess the association between obesity and asthma symptoms or BHR in adults. METHODS: A study was carried out in 1232 people born between 1974 and 1978 in Chile. The participants completed the European Community Health Survey questionnaire, were skin tested and subject to a BHR challenge to methacholine. MEASUREMENTS: Weight, height and waist circumference were measured and body mass index (BMI) was calculated. RESULTS: There was a positive association between wheeze and breathlessness following exercise and BMI (both with an OR 1.03, 95% CI 1.00-1.06), the associations with wheeze tended to disappear in women who did react at least to one allergen, and persisted in those who did not react to any allergens. BMI was negatively associated with BHR (OR 0.93, 95% CI 0.89-0.97). Waist circumference was not associated with asthma symptoms and it was negatively associated with BHR. CONCLUSION: Although there was an association between BMI and asthma symptoms, there were weaknesses in the evidence because waist circumference, a more direct measure of obesity than BMI, was not associated with asthma symptoms, and BMI and waist circumference were negatively associated with BHR.     

Do older adults use the Internet for information on heart attacks? Results from a survey of seniors in King County, Washington

BACKGROUND: Early treatment can reduce mortality from heart attacks. However, patient delay, especially among the elderly, has slowed progress in this area. One of the reasons for delay may be because of a lack of knowledge about symptoms of acute myocardial infarction (AMI) and treatment benefits. The Internet is a new and promising source of heart health information, but we know little about how elderly people use this medium. METHODS: This study investigates the demographic and psychosocial variables that are related to Internet access, health information seeking, and information seeking about heart attacks from the Internet among seniors. We interviewed seniors (N = 323) aged more than 65 years and asked them questions about Internet access, health information seeking, and information seeking on heart attacks, as well as demographic information, risk perceptions for AMI, and personal experience with AMI. RESULTS: The results showed that several demographic variables were related to access to the Internet. Only 7% of the seniors who reported access to the Internet had sought information on heart attacks from the Internet. Age, history of AMI, and family history of AMI were significant predictors of information seeking on heart attacks. This suggests that to date only a very small, high-risk group of seniors actually seeks information on heart attack emergencies from the Internet.     

Can persistent organic pollutants explain the association between serum γ-glutamyltransferase and type 2 diabetes?

The results of several epidemiological studies of serum γ-glutamyltransferase (GGT) led us to hypothesise that associations of GGT within its normal range with type 2 diabetes may reflect detrimental effects of xenobiotics found in the environment, such as persistent organic pollutants (POPs). Epidemiological observations showed that serum GGT activity within its normal range strongly predicted future type 2 diabetes; the predictability of diabetes from obesity was low with GGT at the low end of the normal range; and GGT showed a positive association with known markers of oxidative stress or inflammation. Experimental findings on cellular GGT suggest that serum GGT levels within the normal range may reflect oxidative stress related to the re-synthesis of intracellular glutathione; however, this interpretation is not completely satisfying because, in its role of regenerating intracellular glutathione, GGT activity should be antioxidative. Alternatively, serum GGT activity may reflect amounts of glutathione conjugates formed during the metabolism of xenobiotics. Accordingly, we postulate a two-part hypothesis: that the association of serum GGT with type 2 diabetes reflects exposure to POPs, as these substances, which have a very long half-life, may influence diabetes risk by residing in adipose tissue as endocrine disruptors; and that POPs or similar substances may interact with obesity to cause type 2 diabetes. Supporting this hypothesis, cross-sectional investigation of background exposure to POPs in the National Health and Nutrition Examination Survey showed relationships similar to those observed for GGT, including a powerful association with prevalent diabetes and no association between obesity and diabetes for very low POP concentrations. Our hypothesis can be tested in both prospective studies and toxicological studies.     

Ill or just old? Towards a conceptual framework of the relation between ageing and disease

Background

Is this person ill or just old? This question reflects the pondering mind of a doctor while interpreting the complaints of an elderly person who seeks his help. Many doctors think that ageing is a non-disease. Accordingly, various attempts have been undertaken to separate pathological ageing from normal ageing. However, the existence of a normal ageing process distinct from the pathological processes causing disease later in life can be questioned.

Discussion

Ageing is the accumulation of damage to somatic cells, leading to cellular dysfunction, and culminates in organ dysfunction and an increased vulnerability to death. Analogously, chronic diseases initiate early in life and their development is slow before they become clinically apparent and culminate in disability or death. The definition of disease is also subject to current opinions and scientific understanding and usually, it is an act of individual creativity when physical changes are recognised as symptoms of a new disease. New diseases, however, are only rarely really new. Most new diseases have gone undiagnosed because their signs and symptoms escaped recognition or were interpreted otherwise. Many physical changes in the elderly that are not yet recognised as a disease are thus ascribed to normal ageing. Therefore, the distinction between normal ageing and disease late in life seems in large part arbitrary.

Summary

We think that normal ageing cannot be separated from pathological processes causing disease later in life, and we propose that the distinction is avoided.

     

Can a combination of lifestyle and clinical characteristics explain the presence of foot ulcer in patients with diabetes?

AimsThe aim of this study was to identify the biomechanical, neurological and clinical parameters along with other demographics and lifestyle risk factors that could explain the presence of foot ulcer in patients with diabetes in Africa.MethodsA total of 1270 (M/F:696/574) patients; 77(M/F:53/24) with ulcerated vs 1193 (M/F: 643/550) with non-ulcerated feet; participated in this study. A set of 28 parameters were collected and compared between the participants with and without active foot ulcers. Multivariate logistic regression was utilised to develop an explanatory model for foot ulceration.ResultsFoot swelling (χ2(1,n = 1270) = 265.9,P = 0.000,Phi = 0.464) and impaired sensation to monofilament (χ2(2,n = 1270) = 114.2,P = 0.000,Cramer'sV = 0.300) showed strong association with presence of ulceration. A lower Temperature sensitivity to cold stimuli and limited ankle joint mobility were observed to be significant (P < 0.05) contributors to ulceration. The logistic regression model can justify the presence of foot ulceration with 95.3% diagnostic accuracy, 99.1% specificity and 37.3% sensitivity.ConclusionParticipants with ulcerated foot show distinct characteristics in few foot related parameters. Swollen foot, limited ankle mobility, and peripheral sensory neuropathy were significant characteristics of patients with diabetic foot ulcer. One out of three patients with ulcerated foot showed common characteristics that could be justified by the model.     

Are diabetes and its medications risk factors for the development of COVID-19? Data from a population-based study in Sicily

Background and aimsDiabetes mellitus (DM) has been associated with higher incidence of severe cases of COVID-19 in hospitalized patients, but it is unknown whether DM is a risk factor for the overall COVID-19 incidence. The aim of present study was to investigate whether there is an association of DM with COVID-19 prevalence and case fatality, and between different DM medications and risk for COVID-19 infection and death.Methods and resultsretrospective observational study on all SARS-CoV-2 positive (SARS-CoV-2⁺) cases and deaths in Sicily up to 2020, May 14th. No difference in COVID-19 prevalence was found between people with and without DM (RR 0.92 [0.79–1.09]). Case fatality was significantly higher in SARS-CoV-2⁺ with DM (RR 4.5 [3.55–5.71]). No diabetes medication was associated with differences in risk for SARS-Cov2 infection.Conclusionsin Sicily, DM was not a risk factor for COVID-19 infection, whereas it was associated with a higher case fatality.     

Does genetic risk of obesity modify associations between the neighbourhood environment and body-mass index? A cross-sectional analysis of the UK Biobank dataset

Background

In studies of gene–environment interactions and obesity, the term environment usually refers to individual behavioural factors that influence energy balance. However, evidence suggests that the built environments in which individuals live, work, and play are associated with obesity and may therefore be environmental triggers of genetic risk. No studies have explored whether individual response to such environmental determinants of obesity varies with genetic risk. We aimed to examine whether genetic risk of obesity modifies associations between various neighbourhood characteristics and body-mass index (BMI).