Cognitive and motor perturbations in elderly with longstanding diabetes mellitus.

Type 2 diabetes mellitus is a chronic disease characterized by insulin resistance; inflammation; oxidative stress; vascular damage; and dysfunction of glucose, protein, and lipid metabolisms. However, comparatively less attention has been paid to neurologic alterations seen in elderly individuals with type 2 diabetes. We review clinical, metabolic, and biochemical aspects of diabetic encephalopathy (DE) and propose that quality of dietary lipids is closely linked to DE. This implies that preventive nutritional interventions may be designed to improve DE.

Onset and evolution of nephropathy in rats with spontaneous diabetes mellitus.

The occurrence of renal diabetic complications was studied in diabetic nonobese IIM/FmeSS (eSS) rats. The results were compared with eumetabolic Wistar rats paired by sex and age. Between 6 and 12 months of age, eSS male rats had higher fructosamine values and glucose intolerance as well as increasing proteinuria and uremia. Enhancement in water, calcium and phosphorus fractional excretion with a concomitant lower sodium excretion, was observed from 12 months of age on. 18- and 21-month-old eSS rats exhibited fasting hyperglycaemia and rising values of fructosamine, glucose intolerance and glycosuria. Simultaneously, a notorious worsening of proteinuria as well as alterations in glomerular filtration were verified. Optic microscopy of 12-month-old eSS rat kidneys showed areas of tubular dilatation with protein cylinders. In 21-month-old eSS animals, kidneys appeared overtly damaged. Increased capsular, glomerular and Henle's thin loop diameters were verified in 12- and 21-month-old eSS rats. Glomeruli showed diffuse hypertrophy of mesangial tissue and thickening of the basement membrane. Areas of markedly atrophic and dilated tubules containing acidophilic proteinaceous material were observed. At age of 21 months, kidneys of eumetabolic Wistar control rats presented foci of interstitial and pielic inflammatory infiltrates.

Early lipid alterations in spontaneously diabetic rats.

Human and experimental diabetes mellitus extensively alters lipid metabolism. The eSS is a rat strain that develops a spontaneous diabetes of slow evolution, resembling the non-insulin-dependent diabetes mellitus of young people. We report here disturbances in lipid metabolism of 5-month old eSS rats compared to age-matched alpha-controls. Normal plasmatic glucose levels were found in the fasted state, whereas a diabetic curve was evident for eSS rats after glucose load. Triglyceride content was elevated in plasma and in liver microsomal preparations of eSS animals, when compared to the controls. The diabetic strain revealed a significant fall in the amount of linoleic acid in liver and kidney microsomes and in erythrocyte membranes. In liver, an increase in 22:6 (n-3) was also noted. A depression in the content of linoleic acid as well as an enhancement of docosahexaenoic acid were detected in phosphatidylcholine and phosphatidylethanolamine fractions from liver microsomes of eSS rats. The fatty acid pattern of eSS rat testis showed a raise in the relative percentage of arachidonic and a decrease in 22:5 (n-6), 22:5 (n-3) and 22:6 (n-3) acids compared to their controls. Diabetic rats exhibited a significant increase in microsomal cholesterol content and cholesterol/phospholipid ratio in liver and testis. In the latter tissue, higher values of fluorescence anisotropy were also observed. The current observations indicate that in early stages of the diabetes onset, when eSS rats are still normoglycemic, severe alterations of lipid metabolism may contribute to the establishment and progression of the diabetic syndrome.

Early lipid alterations in spontaneously diabetic rats

Human and experimental diabetes mellitus extensively alters lipid metabolism. The eSS is a rat strain that develops a spontaneous diabetes of slow evolution, resembling the non-insulin-dependent diabetes mellitus of young people. We report here disturbances in lipid metabolism of 5-month old eSS rats compared to age-matched alpha-controls. Normal plasmatic glucose levels were found in the fasted state, whereas a diabetic curve was evident for eSS rats after glucose load. Triglyceride content was elevated in plasma and in liver microsomal preparations of eSS animals, when compared to the controls. The diabetic strain revealed a significant fall in the amount of linoleic acid in liver and kidney microsomes and in erythrocyte membranes. In liver, an increase in 22:6 (n-3) was also noted. A depression in the content of linoleic acid as well as an enhancement of docosahexaenoic acid were detected in phosphatidylcholine and phosphatidylethanolamine fractions from liver microsomes of eSS rats. The fatty acid pattern of eSS rat testis showed a raise in the relative percentage of arachidonic and a decrease in 22:5 (n-6), 22:5 (n-3) and 22:6 (n-3) acids compared to their controls. Diabetic rats exhibited a significant increase in microsomal cholesterol content and cholesterol/phospholipid ratio in liver and testis. In the latter tissue, higher values of fluorescence anisotropy were also observed. The current observations indicate that in early stages of the diabetes onset, when eSS rats are still normoglycemic, severe alterations of lipid metabolism may contribute to the establishment and progression of the diabetic syndrome.

Early lipid alterations in spontaneously diabetic rats

Human and experimental diabetes mellitus extensively alters lipid metabolism. The eSS is a rat strain that develops a spontaneous diabetes of slow evolution, resembling the non-insulin-dependent diabetes mellitus of young people. We report here disturbances in lipid metabolism of 5-month old eSS rats compared to age-matched alpha-controls. Normal plasmatic glucose levels were found in the fasted state, whereas a diabetic curve was evident for eSS rats after glucose load. Triglyceride content was elevated in plasma and in liver microsomal preparations of eSS animals, when compared to the controls. The diabetic strain revealed a significant fall in the amount of linoleic acid in liver and kidney microsomes and in erythrocyte membranes. In liver, an increase in 22:6 (n-3) was also noted. A depression in the content of linoleic acid as well as an enhancement of docosahexaenoic acid were detected in phosphatidylcholine and phosphatidylethanolamine fractions from liver microsomes of eSS rats. The fatty acid pattern of eSS rat testis showed a raise in the relative percentage of arachidonic and a decrease in 22:5 (n-6), 22:5 (n-3) and 22:6 (n-3) acids compared to their controls. Diabetic rats exhibited a significant increase in microsomal cholesterol content and cholesterol/phospholipid ratio in liver and testis. In the latter tissue, higher values of fluorescence anisotropy were also observed. The current observations indicate that in early stages of the diabetes onset, when eSS rats are still normoglycemic, severe alterations of lipid metabolism may contribute to the establishment and progression of the diabetic syndrome. (AU)

Influence of gonadectomy in eSS diabetic rats.

The influence of gonadectomy on some variables related to the diabetic syndrome was studied in the eSS line of rats, a nonobese model of spontaneous non-insulin-dependent diabetes, whose biochemical and histopathological manifestations are more severe in males than in females. Rats were gonadectomized at 90 days of age. Spayed animals showed higher body weight, impaired intolerance to glucose at 9 and 12 months of age, lower insulinemia and a decreased number of large pancreatic islets. Castrated rats revealed lower body weight when compared with controls. However, those males did not evidence impairment in the intolerance to glucose, changes insulinemia or remarkable modifications in endocrine pancreas histology. In kidneys, a lower cellular area in superficial proximal convoluted tubules was noticed. Despite the lower biomass registered in orchidectomized animals, their diabetic evolution was not modified. Conversely, ovariectomy appeared to be a worsening factor.

Effects of dietary sucrose option on the diabetic syndrome of the eSS rat.

The eSS rat is a model of human spontaneous non-insulin-dependent diabetes. Male eSS rats were divided at the age of 4 months into two groups (eSSA and eSSB), both receiving the usual commercial balanced diet with sucrose also made available to eSSA. Sucrose intake did not imply a higher caloric diet, and no differences were found between groups in body weight and plasma triglyceride levels from 6 to 12 months of age. Sucrose option resulted in lower protein, lipid and carbohydrate intakes in eSSA animals. Plasma glucose values were higher in eSSA at different times of the tolerance curve. Likewise, eSSA kidneys showed significantly higher capsular and glomerular diameters and there was a discrete PAS-positive thickening of their basement membrane. We conclude that prolonged ad libitum sucrose intake, without weight gain, causes a moderate metabolic impairment and renal lesions in the eSS diabetic rat.

Intermittent dietary restriction in eSS diabetic rats. Effects on metabolic control and skin morphology.

eSS rats exhibit a non-insulin-dependent diabetic syndrome, significantly influenced by diet. Long-term effects of intermittent dietary restriction were studied in male eSS rats. Experimental animals were fed ad libitum during 48 h and food-deprived the next 24 h (R) while controls (L) of the same strain were freely fed every day. This schedule was maintained from 21 days of age until all rats were sacrificed. R animals were leaner than L rats at 5, 8 and 13 months of age. Moreover, an improved metabolic profile (i.e., lower levels in blood triglycerides, total blood cholesterol, basal blood glucose and blood glucose after an oral glucose load) was found. Histological examination of nuchal skin specimens showed a significant increase of dermal thickness and epidermal hypotrophy in free-fed animals. Collagenous fibers closely packed were found just beneath the dermo-epidermal junction in L rats. This finding was less pronounced in R rats. The above mentioned results suggest that eSS rats would draw advantage from living in environments where food availability is uncertain. The importance of early dietary restrictions in predisposed genotypes appears to be a valuable preventive measure against diabetic evolution and complications.

[Relationship of diet, biomass and expression of diabetes in eSS rats]. / Relación entre dieta, biomasa y expresión de la diabetes en la rata eSS.

The long-term effect of feeding eSS rats three commercial diets on the development of diabetes and its complications has been investigated. These diets differ in their proportions of carbohydrates, fibres, lipids and proteins: diet A is rich in lipids, B in carbohydrates and fibres and C in proteins. However, the proportions of these components lie within the range recommended for rats. Animals receiving diet C showed the highest growth rate and were the first to develop diabetes at the age of four months. They had, moreover, the highest levels of triglycerides, total cholesterol and HDL-cholesterol. Animals fed the A diet were heavier than the other groups at 13 months of age, showing a diabetic glucose tolerance test and the highest values of circulating insulin. They were already diabetic when tested at the age of 6 months. The group fed the B diet remained leaner than the other groups and free of diabetes up to the test performed when they were ten months old. The findings at the age of 23 months were: the A animals developed the largest retroperitoneal and epididymal adipose tissue masses, the C group was the most affected by cataracts which were total, and bilateral in some cases, whereas the B rats were free of them and the A animals showed milder lesions than the C rats. Histological studies of pancreas and kidneys demonstrated that the C animals had fewer Langerhans islands than the other groups and the most severe renal lesions while the B animals had no renal damage. It is concluded that diets leading to overweight, particularly those rich in proteins, make the diabetic syndrome worse in eSS rats.

Relación entre dieta, biomasa y expresión de la diabetes en la rata eSS. / [Relationship of diet, biomass and expression of diabetes in eSS rats]

The long-term effect of feeding eSS rats three commercial diets on the development of diabetes and its complications has been investigated. These diets differ in their proportions of carbohydrates, fibres, lipids and proteins: diet A is rich in lipids, B in carbohydrates and fibres and C in proteins. However, the proportions of these components lie within the range recommended for rats. Animals receiving diet C showed the highest growth rate and were the first to develop diabetes at the age of four months. They had, moreover, the highest levels of triglycerides, total cholesterol and HDL-cholesterol. Animals fed the A diet were heavier than the other groups at 13 months of age, showing a diabetic glucose tolerance test and the highest values of circulating insulin. They were already diabetic when tested at the age of 6 months. The group fed the B diet remained leaner than the other groups and free of diabetes up to the test performed when they were ten months old. The findings at the age of 23 months were: the A animals developed the largest retroperitoneal and epididymal adipose tissue masses, the C group was the most affected by cataracts which were total, and bilateral in some cases, whereas the B rats were free of them and the A animals showed milder lesions than the C rats. Histological studies of pancreas and kidneys demonstrated that the C animals had fewer Langerhans islands than the other groups and the most severe renal lesions while the B animals had no renal damage. It is concluded that diets leading to overweight, particularly those rich in proteins, make the diabetic syndrome worse in eSS rats.

Spontaneous diabetes in eSS rats.

A spontaneous non-insulin-dependent diabetes in a highly inbred line of rats called eSS has been described. It is characterized by early impaired glucose tolerance worsening with age. Males are far more severely affected than females. These animals also exhibit hypertriglyceridemia and hypercholesterolemia. In spite of their hyperglycemia, eSS males have an excess of circulating plasma insulin compared with alpha controls. Eight-month-old eSS males were sensitive to exogenous insulin. Moreover, as the plasma insulin values decrease with age, glucose tolerance is further impaired. An improvement in the metabolic disturbances was registered in diabetic eSS males under long-term food deprivation. Histopathological examination of the pancreas revealed marked changes compared with age-matched controls. The pancreatic islet structure looked disrupted and islets became smaller and more scattered with advancing age. A diffuse glomerulosclerosis, interstitial lymphocyte infiltrates and tubular nephrosis were present in kidneys.