The increasing prevalence of older adults with diabetes has become a major social burden. Diabetes, frailty, and cognitive dysfunction are closely related to the mechanisms of aging. Insulin resistance, arteriosclerosis, chronic inflammation, oxidative stress, and mitochondrial dysfunction may be common mechanisms shared by frailty and cognitive impairment. Hyperglycemia, hypoglycemia, obesity, vascular factors, physical inactivity, and malnutrition are important risk factors for cognitive impairment and frailty in older adults with diabetes. The impact of nutrients on health outcomes varies with age; thus, shifting diet therapy strategies from the treatment of obesity/metabolic syndrome to frailty prevention may be necessary in patients with diabetes who are over 75 years of age, have frailty or sarcopenia, and experience malnutrition. For the prevention of frailty, optimal energy intake, sufficient protein and vitamin intake, and healthy dietary patterns should be recommended. The treatment of diabetes after middle age should include the awareness of proper glycemic control aimed at extending healthy life expectancy with proper nutrition, exercise, and social connectivity. Nutritional therapy in combination with exercise, optimal glycemic and metabolic control, and social participation/support for frailty prevention can extend healthy life expectancy and maintain quality of life in older adults with diabetes mellitus.

Ectodomain shedding (shedding) is a post-translational modification, which liberates the extracellular domain of membrane proteins through juxtamembrane processing executed mainly by the ADAM (a disintegrin and metalloprotease) family of metalloproteases. Because shedding alters characteristics of cells in a rapid and irreversible manner, it should be strictly regulated. However, the molecular mechanisms determining membrane protein susceptibility to shedding (shedding susceptibility) are largely unknown. Here we report that alternative splicing can give rise to both shedding-susceptible and shedding-resistant CADM1 (cell adhesion molecule 1) variant proteins. We further show that O-glycans adjacent to the shedding cleavage site interfere with CADM1 shedding, and the only 33-bp alternative exon confers shedding susceptibility to CADM1 by inserting five non-glycosylatable amino acids between interfering O-glycans and the shedding cleavage site. These results demonstrate that shedding susceptibility of membrane protein can be determined at two different levels of its biosynthesis pathway, alternative splicing and O-glycosylation.

Aim: Selecting optimal energy intake during diet therapy for older patients with diabetes mellitus is difficult because of the large differences in physical function and comorbid diseases. In Japan, although requirements for total energy intake are calculated by multiplying a person's standard bodyweight (BW) by the amount of physical activity, evidence supporting the application of this method among older people is limited. Therefore, we aimed to assess optimal energy intake by evaluating the relationship between energy intake and mortality in older patients.Methods: We evaluated data from a 6‐year prospective follow up of 756 older patients with diabetes mellitus, and the association between baseline nutrient intake and mortality. Total energy intake and nutrients were evaluated, and energy intake per actual BW was categorized into quartiles (Q). Cox regression analysis was used for statistical analyses. Energy intake per standard BW or age‐related target BW was statistically analyzed using the same protocol.Results: Analysis of energy intake per actual BW showed that hazard ratios for mortality was significantly higher in Q1 and Q4. Similar associations were found for energy intake per standard or target BW. Subgroup analysis showed that mortality rate was the lowest in Q2 in the young‐old population and in Q3 in the old‐old population.Conclusions: A U‐shaped relationship was observed between energy intake per BW and mortality in older patients with diabetes mellitus, which suggests that the optimal energy intake per actual or target BW should encompass a wide range to prevent malnutrition and excessive nutrition in these patients. Geriatr Gerontol Int 2020; 20: 59–65.

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