Diabetes mellitus is commonly associated with systolic/diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive control subjects, a heightened plasma insulin response to a glucose challenge is consistently found. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. With the insulin/glucose-clamp technique, in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: Na+ retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth muscle cells. Physiological maneuvers, such as calorie restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; evidence indicates that these maneuvers can also lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia are also associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate-density and low-density lipoproteins, both of which are atherogenic. Last, insulin, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of various growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including non-insulin-dependent diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.

Insulin Resistance: A Multifaceted Syndrome Responsible for NIDDM, Obesity, Hypertension, Dyslipidemia, and Atherosclerotic Cardiovascular Disease

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.29367

The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases.

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.25762

The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association

https://www.gastrojournal.org/article/S0016-5085(05)00694-3/pdf

The Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study

https://aasldpubs.onlinelibrary.wiley.com/doi/epdf/10.1002/hep.21496

The NAFLD fibrosis score: A noninvasive system that identifies liver fibrosis in patients with NAFLD

Background and aims: Fatty liver is a common histological finding in human liver biopsy specimens. It affects 10–24% of the general population and is believed to be a marker of risk of later chronic liver disease. The present study examined the risk of development of cirrhotic liver disease and the risk of death in a cohort diagnosed with pure fatty liver without inflammation. Methods: A total of 215 patients who had a liver biopsy performed during the period 1976–1987 were included in the study. The population consisted of 109 non-alcoholic and 106 alcoholic fatty liver patients. Median follow up time was 16.7 (0.2–21.9) years in the non-alcoholic and 9.2 (0.6–23.1) years in the alcoholic group. Systematic data collection was carried out by review of all medical records. All members of the study cohort were linked through their unique personal identification number to the National Registry of Patients and the nationwide Registry of Causes of Death, and all admissions, discharge diagnoses, and causes of death were obtained. Results: In the non-alcoholic fatty liver group, one patient developed cirrhosis during the follow up period compared with 22 patients in the alcoholic group. Survival estimates were significantly (p Conclusions: This study revealed that patients with type 1 non-alcoholic fatty liver disease have a benign clinical course without excess mortality.

https://gut.bmj.com/content/gutjnl/53/5/750.full.pdf

Long term prognosis of fatty liver: risk of chronic liver disease and death

Systematic literature search for epidemiological evidence for an association of short sleep with weight gain and eventual development of obesity provided 71 original studies and seven reviews of various subsets of these studies We have summarized the evidence for such an association with particular emphasis on prospective studies The studies showed that short sleep duration is consistently associated with development of obesity in children and young adults, but not consistently so in older adults We have identified critical aspects of the evidence, and assessed the possibility for interpretation of the evidence in terms of causality We have discussed the requirement of temporal sequence between putative exposure and outcome and the implications of the time lag between them, the problems in adequate measurements of exposure and effects, the possible bidirectional causal effects, the necessary distinction between confounders and mediators, the possible confounding by weight history, and the possibility of common or upstream underlying causes In conclusion, causal interpretation of the association is hampered by fundamental conceptual and methodological problems Experimental studies may elucidate mechanisms, but adequate coverage of the entire pathway from sleep curtailment through obesity development is not feasible Randomized trials are needed to assess the value of targeted interventions

Short sleep duration as a possible cause of obesity: critical analysis of the epidemiological evidence

Dietary fat intake and weight gain in women genetically predisposed for obesity.

Objective : To examine the association between self reported alcohol intake and subsequent mortality from all causes and if the effect of alcohol intake on the risk of death is modified by sex, age, body mass index, and smoking. Design : Prospective population study with baseline assessment of alcohol and tobacco consumption and body mass index, and 10-12 years9 follow up of mortality. Setting : Copenhagen city heart study, Denmark. Subjects : 7234 women and 6051 men aged 30-79 years. Main outcome measure : Number and time of deaths from 1976 to 1988. Results : A total of 2229 people died, 1398 being men. A U shaped curve described the relation between alcohol intake and mortality. The lowest risk was observed at one to six alcoholic beverages a week (relative risk set at 1). Abstainers had a relative risk of 1.37 (95% confidence interval 1.20 to 1.56) whereas those drinking more than 70 beverages a week had a relative risk of 2.29 (1.75 to 3.00). Among the drinkers, the risk was significantly increased only among those drinking more than 42 beverages a week. Sex, age, body mass index, and smoking did not significantly modify the risk function. The risk among heavy drinkers was slightly reduced when smoking was controlled for. The risk function was similar in the first and second period of six years of observation. Conclusion : Alcohol intake showed a U shaped relation to mortality with the nadir at one to six beverages a week. The risk function was not modified by sex, age, body mass index, or smoking and remained stable over 12 years.

/pdf/influence-of-sex-age-body-mass-index-and-smoking-on-alcohol-3m2whbr4a1.pdf

Influence of sex, age, body mass index, and smoking on alcohol intake and mortality

OBJECTIVE--To assess the relations among prevalence of arterial hypertension, history of weight change, and current body weight in the range from normal weight to severe obesity. DESIGN--Retrospective analysis of medical records of men registered with Danish military authorities from 1943 to 1977 and followed up four to 40 years later. SETTING--Draft board of Copenhagen and surrounding counties and the rest of Sjaelland and surrounding islands. SUBJECTS--964 Men who were severely obese (body mass index greater than or equal to kg/m2 at the first examination) and 1134 random controls. MAIN OUTCOME MEASURES--Blood pressure and weight. RESULTS--Hypertension was more prevalent in subjects with an unchanged body mass index as that index increased over the range studied. At any body mass index hypertension was more prevalent in subjects who had increased to this index and less common in those who had decreased to it than in those who had stayed the same weight since the first examination. Hypertension among controls was most common in those subjects who had become obese during adulthood. CONCLUSIONS--Changes in body weight have a great influence on arterial hypertension independent of the effect of attained weight, particularly in obese subjects.

https://www.bmj.com/content/bmj/299/6702/767.full.pdf

T. I. A. Sørensen

Papers

Long term prognosis of fatty liver: risk of chronic liver disease and death

Short sleep duration as a possible cause of obesity: critical analysis of the epidemiological evidence

Dietary fat intake and weight gain in women genetically predisposed for obesity.

Influence of sex, age, body mass index, and smoking on alcohol intake and mortality

Independent effects of weight change and attained body weight on prevalence of arterial hypertension in obese and non-obese men.