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Diabetes mellitus is a highly prevalent metabolic condition in ageing societies associated with high levels of morbidity, multiple therapies, and functional deterioration that challenges even the best of health care systems to deliver high-quality, individualized care. Most international clinical guidelines have ignored the often-unique issues of frailty, functional limitation, changes in mental health, and increasing dependency that characterize many aged patients with diabetes. A collaborative Expert Group of the IAGG and EDWPOP and an International Task Force have explored the key issues that affect diabetes in older people using a robust method comprising a Delphi process and an evidence-based review of the literature. Eight domains of interest were initially agreed and discussed: hypoglycemia, therapy, care home diabetes, influence of comorbidities, glucose targets, family/carer perspectives, diabetes education, and patient safety. A set of "consensus" statements was produced in each domain of interest. These form a foundation for future policy development in this area and should influence the clinical behavior and approach of all health professionals engaged in delivering diabetes care to older people., (Copyright © 2012 American Medical Directors Association. Published by Elsevier Inc. All rights reserved.)

The klotho gene may be involved in the aging process. Klotho is a coactivator of FGF23, a regulator of phosphate and vitamin D metabolism. It has also been reported to be downregulated in insulin resistance syndromes and paradoxically to directly inhibit IGF-1 and insulin signaling. Our aim was to study klotho's regulation and effects on insulin and IGF-1 signaling to unravel this paradox. We studied klotho tissue distribution and expression by quantitative real-time polymerase chain reaction and Western blotting in obese Zucker rats and high-fat fed Wistar rats, two models of insulin resistance. Klotho was expressed in kidneys but at much lower levels (<1.5%) in liver, muscle, brain, and adipose tissue. There were no significant differences between insulin resistant and control animals. We next produced human recombinant soluble klotho protein (KLEC) and studied its effects on insulin and IGF-1 signaling in cultured cells. In HEK293 cells, FGF23 signaling (judged by FRS2-alpha and ERK1/2 phosphorylation) was activated by conditioned media from KLEC-producing cells (CM-KLEC); however, IGF-1 signaling was unaffected. CM-KLEC did not inhibit IGF-1 and insulin signaling in L6 and Hep G2 cells, as judged by Akt and ERK1/2 phosphorylation. We conclude that decreased klotho expression is not a general feature of rodent models of insulin resistance. Further, the soluble klotho protein does not inhibit IGF-1 and/or insulin signaling in HEK293, L6, and HepG2 cells, arguing against a direct role of klotho in insulin signaling. However, the hypothesis that klotho indirectly regulates insulin sensitivity via FGF23 activation remains to be investigated.

Glucocorticoid therapy (GCT) is commonly used for the treatment of many chronic diseases. It is prescribed in almost 3% of the population > or = 70-years-old. Numerous short- and long-term side effects can occur even at low doses. GCT should be preceded by screening for and stabilization of disorders that can be aggravated by treatment. During GCT regular monitoring for side effects, adjusting of the treatment to the lowest effective dose and regular re-evaluation of the indication are required. The GC withdrawal protocols are not evidence-based and are chosen essentially according to the risk of reactivation of the treated disorder. The risk of secondary adrenal insufficiency is real but quite low, and does not in itself justify the continuation of a GCT.

Elderly diabetic patients are particularly burdened by foot disease. The main causes for foot disease are peripheral neuropathy, foot deformities and peripheral arterial disease (PAD). Other risk factors include poor vision, gait abnormalities, reduced mobility an medical co-morbidities. The risk of major amputations increases with age, along with the increased prevalence of these risk factors. Th true risk of amputation and other burdens of foot disease in the elderly are likely underestimated by current epidemiological data. Th prevalence of neuropathy, foot deformities and PAD as well as the risk of amputation all increase with age even in non-diabetic patients. The principles of prevention and management of diabetic foot disease may also apply to large segments of the elderly non-diabetic population. Foot ulcer prevention relies on the identification of high risk patients and avoidance of triggering events, such as ill-fitting shoes, walking barefoot or poor self-care. PAD is a major cause of amputation and should be prevented by lifelong attention to glycaemic control, treatment of hypertension and dyslipidemia, and avoidance of smoking. The treatment of foot ulcers relies on pressure relief (off-loading), wound debridement, and treatment of infection and ischemia. It requires an individualized approach considering the patient's co-morbidities and functional status. Off-loading remains essential, but devices such as total contact casts or crutches can only rarely be implemented. However, providing adapted standard foot-wear and insisting on its consistent use even at home is often effective. The benefits of aggressive vascular or orthopaedic surgery should be weighed against the risks of prolonged hospitalisation and resulting functional decline. Greater attention to prevention and individualized care are needed to reduce the burden of diabetic foot disease in the elderly.

Postprandial hypotension (PPH) is a clinical entity considered to affect above all elderly people with hypertension. It is equally common in diastolic heart failure, Parkinson's disease, diabetes mellitus and autonomic dysfunction. Diagnosis is based on a minimum of 20 mmHg drop of the systolic blood pressure oron a symptomatic systolic blood pressure decrease within 2 hours of the meal. Post-prandial dizziness, fatigue, syncope and falls must raise suspicion for this entity. Although more frequent than orthostatic hypotension, PPH is less searched for. Socio-economical repercussions associated to falls require a better screening of PPH in hospital and ambulatory conditions.

Background Information: NPY (neuropeptide Y) may have an effect on the properties of vascular endothelial cells such as pro-angiogenic effects and potentiation of noradrenaline-induced vasoconstriction. In HUVEC (human umbilical-vein endothelial cells), immunoreactive neuropeptide Y has been detected, but NPY synthesis, storage and secretion have not been studied. The aim of the present study was to establish NPY expression, storage and cellular transducing effects in HUVEC., Results: HUVEC contain 0.19 fmol of NPY/microg of protein and 0.46 fmol of pro-NPY/microg of protein, as measured by ELISA. RT (reverse transcriptase)-PCR confirmed the expression of NPY in HUVEC. Immunofluorescence revealed the presence of NPY in small punctate structures, with a fluorescence pattern different from that observed for von Willebrand factor, indicating distinct storage compartments. Double labelling for NPY and Rab3A demonstrated similar granular patterns, with at least partial co-localization. Electron microscopy showed NPY immunoreactivity in vesicle-like cytoplasmic structures, of a fine fibrillar texture, as well as in mitochondria and in the nucleus. A similar general distribution pattern was also obtained for Rab3A. Y1 and Y2 receptors were expressed in HUVEC as assessed by RT-PCR, and they were functional since NPY induced a 42 nM intracellular calcium increase within 100 s, representing 22% of the histamine-induced response. In contrast with histamine, NPY did not induce acute von Willebrand factor secretion., Conclusions: HUVEC produce, store and respond to NPY, suggesting an autocrine regulatory role for NPY in the endothelium.

We have analysed the pattern of expression of the hexokinase isoenzyme group in RIN-m5F insulinoma cells. Three hexokinase forms were resolved by DEAE-cellulose chromatography. The most abundant isoenzyme co-eluted with hexokinase type II from rat adipose tissue and displayed a Km for glucose of 0.15 mM, similar to the adipose-tissue enzyme. Hexokinase type II was in large part associated with a particulate subcellular fraction in RIN-m5F cells. The two other hexokinases separated by ion-exchange chromatography were an enzyme similar to hexokinase type I from brain and glucokinase (or hexokinase type IV). The latter isoenzyme was identified as the liver-type glucokinase by the following properties: co-elution with hepatic glucokinase from DEAE-cellulose and DEAE-Sephadex; sigmoid saturation kinetics with glucose with half-maximal velocity at 5.6 mM and Hill coefficient (h) of 1.54; suppression of enzyme activity by antibodies raised against rat liver glucokinase; apparent Mr of 56,500 and pI of 5.6, as shown by immunoblotting after one- and two-dimensional gel electrophoresis; peptide map identical with that of hepatic glucokinase after proteolysis with chymotrypsin and papain. These data indicate that the gene coding for hepatic glucokinase is expressed in RIN-m5F cells, a finding consistent with indirect evidence for the presence of glucokinase in the beta-cell of the islet of Langerhans. On the other hand, the overall pattern of hexokinases is distinctly different in RIN-m5F cells and islets of Langerhans, since hexokinase type II appears to be lacking in islets. Alteration in hexokinase expression after tumoral transformation has been reported in other systems.