Low serum amylase and obesity, diabetes and metabolic syndrome: A novel interpretation

For the last decade, low serum amylase(hypoamylasemia) has been reported in certain common cardiometabolic conditions such as obesity, diabetes(regardless of type), and metabolic syndrome, all of which appear to have a common etiology of insufficient insulin action due to insulin resistance and/or diminished insulin secretion. Some clinical studies have shown that salivary amylase may be preferentially decreased in obese individuals, whereas others have revealed that pancreatic amylase may be preferentially decreased in diabetic subjects with insulin dependence. Despite this accumulated evidence, the clinical relevance of serum, salivary, and pancreatic amylase and the underlying mechanisms have not been fully elucidated. In recent years, copy number variations(CNVs) in the salivary amylase gene(AMY1), which range more broadly than the pancreatic amylase gene(AMY2A and AMY2B), have been shown to be well correlated with salivary and serum amylase levels. In addition, low CNV of AMY1, indicating low salivary amylase, was associated with insulin resistance, obesity, low taste perception/satiety, and postprandial hyperglycemia through impaired insulin secretion at early cephalic phase. In most populations, insulin-dependent diabetes is less prevalent(minor contribution) compared with insulin-independent diabetes, and obesity is highly prevalent compared with low body weight. Therefore, obesity as a condition that elicits cardiometabolic diseases relating to insulin resistance(major contribution) may be a common determinant for low serum amylase in a general population. In this review, the novel interpretation of low serum, salivary, and pancreas amylase is discussed in terms of major contributions of obesity, diabetes, and metabolic syndrome.

Unhealthy eating habits around sleep and sleep duration: To eat or fast?

Traditionally, breakfast skipping(BS), and recently latenight dinner eating(LNDE), have attracted attention in public health because they can predispose to cardiometabolic conditions such as obesity and type 2 diabetes. Intriguingly, it has become evident that short duration of sleep elicits similar health risks. As LNDE, BS, and short sleep can be closely related and can aggravate each other, these three should not be considered separately. In this context, LNDE(or its equivalents, snacking or heavy alcohol consumption after dinner) and BS may be representative unhealthy eating habits around sleep(UEHAS). While it is important to take energy in the early morning for physical and intellectual activities, attaining a fasting state is essential for metabolic homeostasis. Our previous UEHAS studies have shown that BS without LNDE, i.e., BS alone, is not associated with obesity and diabetes, suggesting the possibility that BS or taking a very low energy breakfast, which could yield fasting for a while, may prevent obesity and diabetes in people with inevitable LNDE. Further studies considering UEHAS and short sleep simultaneously are needed to elucidate the effects of these unhealthy lifestyles on cardiometabolic diseases.

Age-dependent changes in the association between sleep duration and impaired glucose metabolism

AIM To investigate whether the association between sleep duration and impaired glucose metabolism varies among younger and older populations.METHODS We reviewed data of self-reported habitual sleep duration per night, HbA1c levels, and clinically relevant factors in a cross-sectional checkup database of 75472 Japanese from the general population aged 20-79 years(51695 men and 23777 women). Associations of prediabetes(HbA1c ≥ 5.7% and/or diabetic pharmacotherapy) or diabetes(HbA1c ≥ 6.5% and/or diabetic pharmacotherapy) with short and long sleep durations compared with a reference sleep duration(7 h) were investigated by multivariate logistic regression analysis. We controlled for potential relevant confounders, including age, sex, and work duration per day according to younger and older subjects.RESULTS As age advanced, sleep duration became longer and this increase in the 40 s and 50 s was two times greater in men than in women. This finding was accompanied by a deterioration in HbA1c levels. In subjects aged youngerthan 40 years(n = 32929), HbA1c levels were inversely and linearly correlated with sleep duration in both sexes. However, in subjects aged 40 years or older(n = 42543), HbA1c levels showed a non-linear relationship against sleep duration with a nadir at 7 h. Multivariate logistic regression analysis showed that in younger subjects, short durations of sleep(≤ 5 h and 6 h) were positively associated with prediabetes(both P < 0.001), but a long duration of sleep(≥ 8 h) was inversely associated with prediabetes(P < 0.001). These associations remained significant after adjustment for relevant confounders, including age, sex, and work duration per day(ORs = 1.20, 95%CI: 1.05-1.37, P < 0.001; ORs = 1.12, 95%CI: 1.02-1.24, P < 0.05; and ORs = 0.84, 95%CI: 0.72-0.99, P < 0.05, respectively). In contrast, in older subjects, besides an association of prediabetes with a short duration of sleep(≤ 5 h)(ORs = 1.12, 95%CI: 1.03-1.21, P < 0.01), diabetes was significantly associated with a long duration of sleep(≥ 8 h)(ORs = 1.11, 95%CI: 1.02-1.25, P < 0.05). CONCLUSION A short sleep duration may be associated with prediabetes throughout life. However, the association between a long sleep duration and glucose metabolism can change with aging.

Design of the Saitama Cardiometabolic Disease and Organ Impairment Study (SCDOIS): A Multidisciplinary Observational Epidemiological Study

Background: In the past few decades, the incidence of cardiometabolic diseases and disorders of the liver, kidney, pancreas, heart, and lung, have been increasing in Western and Asian countries, including Japan. Numerous factors, including abnormal body weight (obesity, overweight, or underweight), infrequent exercise, and other unfavorable lifestyle factors (e.g., smoking and heavy alcohol drinking) have been proposed as risk factors for the development and the progression of diseases, such as type 2 diabetes, hypertension, and dyslipidemia, which ultimately lead to impaired organ function and possibly death. However, the mechanisms that link these risk factors with diseases are still poorly understood, and the potential treatments, including pharmacotherapy and diet, have not been fully evaluated. Methods: In 2011, we established a new collaborative research program, the Saitama Cardiometabolic Disease and Organ Impairment Study (SCDOIS). This multidisciplinary observational epidemiological research study was designed to cover several high-profile diseases and some traditional fields of internal medicine, as well as apparently unrelated fields and particular lifestyle factors, such as unhealthy eating behaviors. In a series of studies, apparently healthy subjects who underwent a regular medical checkup were retrospectively identified based on the results of their medical checkups. In this way, the incidence, prevalence, causality, and clinical relevance of specific conditions and diseases have been investigated in cross-sectional analyses of 100,000 - 200,000 adults, and in longitudinal studies of several thousand subjects who underwent medical checkups multiple times. Discussion: This article describes the background, rationale, purpose, and methods of the SCDOIS. Using data obtained from annual medical checkups, our goals are to 1) establish criteria or identify clinical features that would enable clinicians to detect the presence of abnormal conditions associated with cardiometabolic diseases and/or organ impairment much earlier in the disease course;and 2) determine the potential mechanisms and therapies for these conditions.

Vague relationship between alcohol consumption and metabolic syndrome in nonobese people

Fatty liver, including non-alcoholic fatty liver disease, is closely associated with metabolic syndrome (MS). Thus, the presence of fatty liver without MS in some conditions may be clinically important. Many studies have shown that compared with no or occasional alcohol intake, moderate alcohol consumption is associated with lower prevalence rates of hypertension and type 2 diabetes, and lower levels of circulating C-reactive protein, a valuable marker for MS and insulin resistance. Considering these findings, light to moderate alcohol consumption has theoretical benefits on fatty liver and MS. Fatty liver, including non-alcoholic fatty liver disease, may be more clinically important than MS, particularly in non-obese individuals, because fatty liver can develop before MS in several conditions, such as regular alcohol consumers. Furthermore, most of the currently used MS criteria are unable to detect "true MS" because of variations in multiple factors such as age, height, medications, and complications.

Fasting biochemical hypoglycemia and related-factors in nondiabetic population: Kanagawa Investigation of Total Check-up Data from National Database-8

BACKGROUND In healthy people,the lowest daily blood glucose concentration is usually observed in the early morning,after overnight fasting.However,the clinical relevance and the prevalence of fasting biochemical hypoglycemia(FBH)are poorly understood in people who do not have diabetes,although the clinical implications of such hypoglycemia have been extensively studied in patients with diabetes.FBH can be influenced by many factors,including age,sex,body mass,smoking,alcohol drinking,exercise levels,medications,and eating behaviors,such as breakfast skipping and late-night eating.AIM To determine the prevalence of FBH and investigated its association with potential risk factors in a population without diabetes.METHODS Clinical parameters and lifestyle-related factors were assessed in a cross-sectional study of 695613 people aged 40-74 years who had undergone a health check-up(390282 men and 305331 women).FBH was defined as fasting plasma glucose<70 mg/dL(3.9 mmol/L)after overnight fasting,regardless of any symptoms.The absence of diabetes was defined as HbA1c<6.5%,fasting plasma glucose<126 mg/dL(7.0 mmol/L),and no pharmacotherapy for diabetes.Multivariate logistic regression analysis,with adjustment for confounding factors,was used to identify associations.RESULTS FBH was present in 1842 participants(0.26%).There were significantly more women in the FBH group(59.1%)than in the non-FBH group(43.9%).Values of most of the clinical parameters,but not age,were significantly lower in the FBH group than in the non-FBH group.Logistic regression analysis showed that a body mass index of≤20.9 kg/m2(reference:21-22.9 kg/m2)and current smoking were significantly associated with FBH,and this was not altered by adjustment for age,sex,and pharmacotherapy for hypertension or dyslipidemia.Female sex was associated with FBH.When the data were analyzed according to sex,men in their 60s or 70s appeared more likely to experience FBH compared with their 40s,whereas men in their 50s and women aged≥50 years appeared less likely to experience FBH.The relationships of FBH with other factors including alcohol drinking and pharmacotherapies for hypertension and dyslipidemia also differed between men and women.CONCLUSION FBH occurs even in non-diabetic people,albeit at a very low frequency.FBH is robustly associated with low body mass and smoking,and its relationship with lifestyle factors varies according to sex.