Aims/Introduction
To investigate the prevalence of sarcopenia, its related factors and indicators of physical evaluation in elderly diabetes patients.
Materials and Methods
This was a cross‐sectional ...observation study. A total of 267 diabetes patients (159 men, 108 women) aged >65 years were recruited in the present study. Skeletal muscle mass index, grip strength and usual gait speed were measured to diagnose sarcopenia according to the Asian Working Group for Sarcopenia. Body composition was measured using bioelectrical impedance analysis. Body mass index (BMI) and body fat percentage were evaluated in quartiles to investigate the relationship with sarcopenia. A multiple logistic regression analysis examined sarcopenia‐related factors.
Results
The prevalence of sarcopenia in all participants was 18.7% and increased with age. Sarcopenia decreased as BMI increased (P < 0.01, Cochran–Armitage test). In contrast, the third quartile body fat percentage group showed the lowest prevalence of sarcopenia. A strong positive correlation was observed between body mass and skeletal muscle mass indices (R = 0.702–0.682). Multiple logistic regression analysis showed that sarcopenia was associated with lower BMI, non‐use of metformin and lower bone mineral content in men (P < 0.05), and lower bone mineral content, lower serum levels of albumin and older age in women (P < 0.05).
Conclusions
The present study suggests that diabetes patients with a high body fat percentage in addition to low BMI might develop sarcopenia. It is suggested that physical management in elderly diabetes patients should be carried out based on the evaluation of BMI and body fat percentage to prevent sarcopenia.
We demonstrated that cross‐sectional observation study investigated the prevalence of sarcopenia, its related factors, and indicators of physical evaluation in elderly diabetic patients.The prevalence of sarcopenia showed decreasing trend as body mass index increased in both sexes, in contrast, the third quartile body fat percentage group exhibited the lowest prevalence of sarcopenia. The results of the body composition analysis highlight the importance of evaluating the balance between skeletal muscle mass index and body fat percentage rather than evaluating by body mass index alone to manage the physical of elderly diabetic patients.
Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone that has an antioxidative protective effect on various tissues. Here, we determined whether GLP-1 has a role in the pathogenesis of diabetic ...nephropathy using nephropathy-resistant C57BL/6-Akita and nephropathy-prone KK/Ta-Akita mice. By in situ hybridization, we found the GLP-1 receptor (GLP-1R) expressed in glomerular capillary and vascular walls, but not in tubuli, in the mouse kidney. Next, we generated C57BL/6-Akita Glp1r knockout mice. These mice exhibited higher urinary albumin levels and more advanced mesangial expansion than wild-type C57BL/6-Akita mice, despite comparable levels of hyperglycemia. Increased glomerular superoxide, upregulated renal NAD(P)H oxidase, and reduced renal cAMP and protein kinase A (PKA) activity were noted in the Glp1r knockout C57BL/6-Akita mice. Treatment with the GLP-1R agonist liraglutide suppressed the progression of nephropathy in KK/Ta-Akita mice, as demonstrated by reduced albuminuria and mesangial expansion, decreased levels of glomerular superoxide and renal NAD(P)H oxidase, and elevated renal cAMP and PKA activity. These effects were abolished by an adenylate cyclase inhibitor SQ22536 and a selective PKA inhibitor H-89. Thus, GLP-1 has a crucial role in protection against increased renal oxidative stress under chronic hyperglycemia, by inhibition of NAD(P)H oxidase, a major source of superoxide, and by cAMP-PKA pathway activation.
The role of stromal cell–derived factor-1 (SDF-1) in the pathogenesis of diabetic nephropathy and its modification by dipeptidyl peptidase-4 (DPP-4) inhibition are uncertain. Therefore, we studied ...this independent of glucagon-like peptide-1 receptor (GLP-1R) signaling using two Akita diabetic mouse models, the diabetic-resistant C57BL/6-Akita and diabetic-prone KK/Ta-Akita. Increased SDF-1 expression was found in glomerular podocytes and distal nephrons in the diabetic-prone mice, but not in kidneys from diabetic-resistant mice. The DPP-4 inhibitor linagliptin, but not the GLP-1R agonist liraglutide, further augmented renal SDF-1 expression in both Glp1r+/+ and Glp1r–/– diabetic-prone mice. Along with upregulation of renal SDF-1 expression, the progression of albuminuria, glomerulosclerosis, periglomerular fibrosis, podocyte loss, and renal oxidative stress was suppressed in linagliptin-treated Glp1r+/+ diabetic-prone mice. Linagliptin treatment increased urinary sodium excretion and attenuated the increase in glomerular filtration rate which reflects glomerular hypertension and hyperfiltration. In contrast, selective SDF-1 receptor blockade with AMD3100 reduced urinary sodium excretion and aggravated glomerular hypertension in the Glp1r+/+ diabetic-prone mice. Thus, DPP-4 inhibition, independent of GLP-1R signaling, contributes to protection of the diabetic kidney through SDF-1–dependent antioxidative and antifibrotic effects and amelioration of adverse renal hemodynamics.
A 67-year-old man with type 1 diabetes, Cronkhite-Canada syndrome, and membranous nephropathy who received insulin therapy was admitted to our hospital with right hemiplegia and dysarthria. Brain ...magnetic resonance imaging revealed a lesion with a high diffusion-weighted imaging signal and low apparent diffusion coefficient signal in the posterior limb of the left internal capsule. He was hypoglycemic with a blood glucose level of 56 mg/dL (3.1 mmol/L). Following glucose administration, the patient’s symptoms resolved within several hours. The patient experienced similar transient hypoglycemic hemiplegia at midnight, three times within 10 days. In a literature review of 170 cases of hypoglycemic hemiplegia, 26 cases of recurrent hemiplegia were investigated. Recurrent hypoglycemic hemiplegia occurs more frequently on the right side than on the left side, and most recurrences occur within approximately a week, almost exclusively at midnight and in the early morning. We speculate that hypoglycemia-associated autonomic failure may be involved in the nocturnal recurrence of episodes. In our patient, depleted endogenous insulin secretion and lipodystrophy at the injection site, may have acted as additional factors, leading to severe hypoglycemia despite the absence of apparent autonomic neuropathy. Clinically, it is important to recognize hypoglycemia as a cause of hemiplegia to avoid unnecessary intervention and to maintain an appropriate blood glucose level at midnight and early in the morning to prevent recurrent hypoglycemic hemiplegia.
The crosstalk between sodium-glucose cotransporter 2 (SGLT2) inhibition and a membrane-associated endocytic receptor megalin function involved in renal proximal tubular protein overload in ...progressive diabetic nephropathy (DN) is uncertain. Here, we determined whether SGLT2 inhibition affects megalin endocytic function through suppressing its O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) and protects the diabetic kidney from protein overload.
We treated 8-week-old male non-obese and hypoinsulinemic KK/Ta-Ins2Akita (KK/Ta-Akita) mice which develop progressive DN with an SGLT2 inhibitor ipragliflozin or insulin for 6 weeks, and investigated the endocytic function (proximal tubular protein reabsorption), renal expression and O-GlcNAcylation of megalin along with their effects on renal phenotypes including histology and biochemical markers.
The treatment with ipragliflozin, but not insulin, suppressed megalin O-GlcNAcylation and accelerated its internalization, resulting in reduction in proximal tubular reabsorption of the highly filtered plasma proteins such as albumin and neutrophil gelatinase-associated lipocalin. These alterations following the ipragliflozin treatment contributed to amelioration of proximal tubular protein overload, mitochondrial morphological abnormality, and renal oxidative stress and tubulointerstitial fibrosis.
The present study provides a novel crosstalk mechanism between SGLT2 inhibition and megalin underlying the potential renal benefits of SGLT2 inhibition in DN.
•SGLT2 inhibition suppresses renal proximal tubule megalin O-GlcNAcylation.•Diminished O-GlcNAcylation promotes proximal tubule megalin internalization.•Proximal tubule megalin internalization reduces its endocytic function.•Reduced megalin endocytic function ameliorates renal protein overload in diabetes.•Amelioration of protein overload attenuates proximal tubule mitochondrial injury.
Aims/Introduction
Pharmacological levels of glucagon‐like peptide‐1 (GLP‐1) can decelerate gastric emptying (GE) and reduce postprandial glucose levels. Most previous studies have used liquid meals ...to evaluate GE. We evaluated the effects of GLP‐1 receptor agonists (GLP‐1 RAs) on GE and postprandial glucose excursion in Japanese type 2 diabetes mellitus patients using a combination of solid and liquid meals.
Materials and Methods
In this single‐center, prospective, open‐label study, nine healthy individuals and 17 patients with type 2 diabetes mellitus consumed a 460‐kcal combination of a solid and liquid meal labeled with 13C‐acetic acid. GE was measured from t = 0 to 150 min in a continuous 13C breath test. Eight participants with type 2 diabetes mellitus were administered GLP‐1 RAs, and we examined the relationship between GE and blood glucose excursion.
Results
There were no differences in the average GE coefficient (GEC) and lag time between the healthy and type 2 diabetes mellitus groups. However, the type 2 diabetes mellitus group showed larger GEC variations (P < 0.05). The coefficient of variation of R‐R intervals was a significant predictor of GEC in type 2 diabetes mellitus patients (P < 0.01). The short‐acting GLP‐1 RA reduced the GEC at 1 month (P = 0.012), whereas the long‐acting GLP‐1 RA did not significantly change the GEC after treatment. A positive relationship was observed between postprandial glucose excursion from T0 min to T60 min and the GEC (r2 = 0.75; P < 0.01).
Conclusions
The reduction in GE rate by the administration of GLP‐1 RAs can predict the improvement in postprandial glucose excursion in type 2 diabetes mellitus patients.
The purpose of this research was to evaluate the effect of glucagon‐like peptide‐1 receptor agonists on gastric emptying and postprandial glucose excursion in Japanese patients with type 2 diabetes mellitus using both liquid and solid meals. We revealed that the reduction in gastric emptying by the administration of glucagon‐like peptide‐1 receptor agonists can predict the improvement in postprandial glucose excursion in type 2 diabetes mellitus patients, using a combination of liquid and solid meals, and a continuous 13C breath test.
Superoxide dismutase (SOD) is a major antioxidant enzyme for superoxide removal, and cytoplasmic SOD (SOD1) is expressed as a predominant isoform in all cells. We previously reported that renal SOD1 ...deficiency accelerates the progression of diabetic nephropathy (DN) via increasing renal oxidative stress. To evaluate whether the degree of SOD1 expression determines regeneration capacity and sarcopenic phenotypes of skeletal muscles under incipient and advanced DN conditions, we investigated the alterations of SOD1 expression, oxidative stress marker, inflammation, fibrosis, and regeneration capacity in cardiotoxin (CTX)-injured tibialis anterior (TA) muscles of two Akita diabetic mouse models with different susceptibility to DN, DN-resistant C57BL/6-Ins2Akita and DN-prone KK/Ta-Ins2Akita mice. Here, we report that KK/Ta-Ins2Akita mice, but not C57BL/6-Ins2Akita mice, exhibit delayed muscle regeneration after CTX injection, as demonstrated by the finding indicating significantly smaller average cross-sectional areas of regenerating TA muscle myofibers relative to KK/Ta-wild-type mice. Furthermore, we observed markedly reduced SOD1 expression in CTX-injected TA muscles of KK/Ta-Ins2Akita mice, but not C57BL/6-Ins2Akita mice, along with increased inflammatory cell infiltration, prominent fibrosis and superoxide overproduction. Our study provides the first evidence that SOD1 reduction and the following superoxide overproduction delay skeletal muscle regeneration through induction of overt inflammation and fibrosis in a mouse model of progressive DN.
Although the measurement of hemoglobin A1c (HbA1c) using high-performance liquid chromatography (HPLC) is routinely used to estimate average blood glucose levels, it may not be accurately measured ...for various reasons, such as alteration of red blood cell lifespan and the existence of hemoglobin variants; including hemoglobin F (HbF). Here, we report cases of fulminant type 1 and type 2 diabetes mellitus in which HbA1c levels were unmeasurable because of increased labile HbA1c levels. Case 1 involved a 73-year-old man with fulminant type 1 diabetes mellitus, who was brought to our hospital with diabetic ketoacidosis. The patient’s blood glucose level was 994 mg/dL, and HbA1c was unmeasurable, which turned out to be 6.2% on the next day when the blood glucose level was normalized. Case 2 involved a 72-year-old man with type 2 diabetes mellitus, whose blood glucose level was 767 mg/dL, and HbA1c was unmeasurable, which turned out to be 17.9% the following day. In both cases, the chromatograms showed that the HbA1c peaks overlapped with large labile HbA1c peaks, which decreased the next day. It is important to keep in mind that HbA1c levels may not be accurately measured in cases of extreme hyperglycemia because of an increase in labile HbA1c, regardless of the absolute HbA1c level.
Caloric restriction (CR) promotes longevity and exerts anti-aging effects by increasing Sirtuin production and activation. Gastric inhibitory polypeptide (GIP), a gastrointestinal peptide hormone, ...exerts various effects on pancreatic β-cells and extra-pancreatic tissues. GIP promotes glucose-dependent augmentation of insulin secretion and uptake of nutrients into the adipose tissue.
Gipr-/- and Gipr+/+ mice were used for lifespan analysis, behavior experiments and gene expression of adipose tissue and muscles. 3T3-L1 differentiated adipocytes were used for Sirt1 and Nampt expression followed by treatment with GIP and α-lipoic acid.
We observed that GIP receptor-knockout (Gipr-/-) mice fed normal diet showed an extended lifespan, increased exploratory and decreased anxiety-based behaviors, which are characteristic behavioral changes under CR. Moreover, Gipr-/- mice showed increased Sirt1 and Nampt expression in the adipose tissue. GIP suppressed α-lipoic acid-induced Sirt1 expression and activity in differentiated adipocytes.
Although maintenance of CR is difficult, food intake and muscle endurance of Gipr-/- mice were similar to those of wild-type mice. Inhibition of GIP signaling may be a novel strategy to extend the lifespan of diabetic patients.
•Caloric restriction (CR) promotes longevity and exerts anti-aging effects by increasing Sirtuin production and activation.•Gastric inhibitory polypeptide (GIP), a gastrointestinal peptide hormone, exerts various effects on extra-pancreatic tissues.•GIP receptor-knockout (Gipr−/-) mice fed normal diet showed an extended lifespan, increased exploratory behaviors.•Gipr−/- mice showed increased Sirt1 and Nampt expression in the adipose tissue.•Inhibition of GIP signaling may be a novel strategy to extend the lifespan of diabetic patients.
Renal superoxide excess, which is induced by an imbalance of the superoxide-producing enzyme NAD(P)H oxidase and the superoxide-scavenging enzyme superoxide dismutase (SOD) under hyperglycemia, ...increases oxidative stress and contributes to the development of diabetic nephropathy. In this study, we treated non-obese and hypoinsulinemic C57BL/6-Ins2(Akita) (C57BL/6-Akita) diabetic mice with telmisartan (5 mg kg(-1) per day), an angiotensin II type 1 receptor blocker, or amlodipine (5 mg kg(-1) per day), a calcium channel blocker, for 4 weeks and compared the effects of these two anti-hypertensive drugs on renal NAD(P)H oxidase, SOD and transcription factor Nrf2 (NF-E2-related factor 2), which is known to upregulate several antioxidant enzymes including SOD. Vehicle-treated C57BL/6-Akita mice exhibited higher renal NAD(P)H oxidase and lower renal SOD activity with increased levels of renal superoxide than the C57BL/6-wild-type non-diabetic mice. Interestingly, telmisartan treatment not only reduced NAD(P)H oxidase activity but also enhanced SOD activity in C57BL/6-Akita mouse kidneys, leading to a reduction of renal superoxide levels. Furthermore, telmisartan-treated C57BL/6-Akita mice increased the renal protein expression of SOD and Nrf2. In parallel with the reduction of renal superoxide levels, a reduction of urinary albumin levels and a normalization of elevated glomerular filtration rate were observed in telmisartan-treated C57BL/6-Akita mice. In contrast, treatment with amlodipine failed to modulate renal NAD(P)H oxidase, SOD and Nrf2. Finally, treatment of C57BL/6-Akita mice with apocynin, an NAD(P)H oxidase inhibitor, also increased the renal protein expression of SOD and Nrf2. Collectively, our data suggest that NAD(P)H oxidase negatively regulates renal SOD, possibly by downregulation of Nrf2, and that telmisartan could upregulate renal SOD by the suppression of NAD(P)H oxidase and subsequent upregulation of Nrf2, leading to the amelioration of renal oxidative stress and diabetic renal changes.
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