Abstract Aim This article is an update of the relationship between type 2 diabetes (T2D), cognitive dysfunction and dementia in older people. Methods and results The number of older patients ...consulting for diabetes who also exhibit cognitive difficulties is consistently growing because of the increased longevity of the population as a whole and, according to a number of studies, the increased risk of cognitive impairment and dementia in older diabetic patients. Many studies have demonstrated a link between poor glucose control and deteriorated cognitive function in diabetic patients. A history of severe hypoglycaemic episodes has also been associated with a greater risk of late-in-life cognitive deficits and dementia in patients with T2D. Several processes are thought to promote cognitive decline and dementia in diabetics. Based on both clinical and non-clinical findings, the factors most likely to alter brain function and structure are cerebrovascular complications of diabetes, alterations in glucose and insulin, and recurrent hypoglycaemia. Together with other diabetes complications, cognitive deficits contribute to functional impairment, increased frequency of depression-related symptoms, greater incidence of recurrent hypoglycaemia, poorer adherence to treatment and, finally, poorer prognosis, as evidenced by recent longitudinal studies. Conclusion Clinical guidelines have recently been devised for older diabetic patients, particularly those with cognitive deficits and a reduced capacity to self-manage. In the most vulnerable patients, specific treatment strategies have been proposed for glycaemic control to limit metabolic decompensation and avoid the risk of hypoglycaemia. Educational measures, provided mainly to maintain patient autonomy and avoid hospital admission, have also been adapted according to patients’ cognitive and functional status.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Recognizing the role of dysglycaemia, ‘ambient’ hyperglycaemia, ‘metabolic memory’ and glycaemic variability as risk factors for macrovascular diseases is mandatory for effective diabetes management. ...Chronic hyperglycaemia, also referred to as ‘ambient hyperglycaemia’, was only fully acknowledged as a risk factor for adverse cardiovascular events when the beneficial effects of intensive glucose-lowering strategies were consolidated in the extended follow-up (> 10 years) of patients included in the United Kingdom Prospective Diabetes Study (UKPDS) and Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study. These studies led to the concept of the glucose-lowering ‘legacy effect’ (metabolic memory), which depends on the duration and magnitude of glucose-lowering, and is not a ‘forever’ phenomenon, as demonstrated in the 15-year follow-up of the Veterans Affairs Diabetes Trial (VADT). The relatively weak evidence for linking long- and short-term glycaemic variability to vascular complications in patients with diabetes is mainly due to a reliance on observational and retrospective studies, and the lack of randomized interventional trials. However, hypoglycaemia may play an intermediary role in accentuating the link between glycaemic variability and vascular events.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Abstract Aim The current sudomotor function tests are too time-consuming to be used for diabetic patients in daily practice. EZSCAN is a new, patented technology that measures electrochemical skin ...conductance (ESC) through reverse iontophoresis and chronoamperometry. The aim of the present study was to assess the sensitivity, specificity and reproducibility of the method in type 2 diabetic patients in comparison to control subjects with no risk of diabetes. Methods A total of 133 type 2 diabetic patients and 41 control subjects were tested. Participants placed their hands and feet on nickel electrodes, and an incremental low direct current was applied to the anode for 2 min. ESC was calculated from the resulting voltage and generated current. ESC diagnostic accuracy was analyzed by ROC curve modeling, and reproducibility was assessed using Bland–Altman analysis. Results The ESC of hands and feet was significantly reduced in diabetic patients (53 ± 16 μSi and 67 ± 14 μSi, respectively) compared with control subjects (68 ± 16 μSi and 80 ± 7 μSi, respectively; P < 0.0001). ESC values had a sensitivity of 75% and specificity of 100%, with an area under the ROC curve of 0.88 at a threshold of 50% on the EZSCAN scale. Coefficients of variation in hand and foot measurements were 15 and 7%, respectively. Conclusion The good sensitivity, specificity and reproducibility of EZSCAN make it a feasible alternative for assessing sudomotor dysfunction, a clinical manifestation of autonomic neuropathy in diabetic patients. The test takes < 3 min to perform, and requires neither special patient preparation nor medical personnel training.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
The role of glycaemic control in the mortality of elderly diabetic patients remains uncertain. GERODIAB is the first multi-centre, prospective, observational study that aims to describe the link ...between HbA1c and 5-year mortality in French, type 2 diabetic patients aged ≥70 years.
Consecutive patients (n=987; mean age 77 years) were included from 56 diabetes centres and followed for five years. Individual histories, risk factors, standard diabetes parameters and geriatric evaluations were regularly recorded. Survival was studied using the Kaplan–Meier method. Multivariable analyses used Cox regression.
Twenty-one percent of the patients died, 13% were lost during follow-up. Patients with a 5-year mean HbA1c in the range 40–50) mmol/mol (5.8–6.7) %) had the highest survival (84%); those in the range 50–70) mmol/mol (6.7–8.6) %) or <40mmol/mol (<5.8%) an intermediary survival rate (79%); patients with HbA1c ≥70mmol/mol (≥8.6%) the worst survival (71%). Patients with mean HbA1c ≥70mmol/mol (≥8.6%) had a significantly higher mortality than those with lower HbA1c (P=0.011), and HbA1c remained a significant predictor of mortality after adjusting for individual, diabetic and geriatric factors (hazards ratio 95%CI: 1.76 1.21 to 2.57, P=0.0033). Survival was also significantly associated with both HbA1c variability and with the frequency of HbA1c determinations.
In this large sample of elderly French type 2 diabetic patients, an HbA1c level <70mmol/mol (<8.6%) was associated with lower mortality. The range 40–50) mmol/mol (5.8–6.7) %) could be an acceptable target provided patients are not exposed to hypoglycaemia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Abstract Aim The aim of this paper is to provide the fundamental background of the inflammation theory associated with type 2 diabetes, to discuss the clinical consequences of low-grade inflammation, ...particularly in terms of cardiovascular risk, and to infer some clinical therapeutic strategies deriving from drugs that already exist or are in development. Methods This non-exhaustive work is the result of a Pubmed® research, based on requests including the following keywords: diabetes, inflammation, innate immunity, obesity, reticulum endoplasmic stress, cytokines, endothelial dysfunction. Results Obesity and type 2 diabetes are linked with a low-grade inflammation state that reflects the activation of innate immunity where metabolic, environmental and genetic factors are implicated. The role of endoplasmic reticulum stress and unfold protein response is underlined. Inflammation markers are predictive for the risk to develop diabetes, and are associated with an increased cardiovascular risk. While lifestyle modifications are followed by an improvement in inflammation markers, treatments inferred from the inflammation theory are of great interest, although quite moderate effects on glycaemic control have been observed with some of them. Conclusion The development of molecules targeting different inflammatory mechanisms could lead in diabetic patients to improvement of both glycaemia and cardiovascular prognosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Abstract Aim Cardiovascular autonomic neuropathy (CAN) is a common but often overlooked complication of diabetes. Sympathetic C-fibers innervating sweat glands can be impaired early on in patients ...with diabetes. In this study, SUDOSCAN, a new non-invasive device that assesses sudomotor function was compared to methods generally used for the investigation of CAN. Patients A total of 232 patients with diabetes were measured for heart rate variability (HRV) at rest and during moderate activity. Time and frequency domain analysis techniques, including measurement of the low-frequency (LF) domain component, were assessed during HRV testing. Ewing tests, as recommended by the French Health Authority, were also done. Electrochemical sweat conductance (ESC) was measured on the hands and feet, and a risk-score was calculated. Results Using two abnormal Ewing tests as a reference for the area under the curve (AUC) of the receiver operating characteristics (ROC) curve for SUDOSCAN, the risk-score was 0.74, with a sensitivity of 92% and specificity of 49% for a risk-score cut-off value of 35%. For the ROC curve analysis using the LF power component during moderate activity at a threshold of 90 ms2 (first quartile) as reference, the AUC was higher for the SUDOSCAN risk-score (0.77) compared with the standard Ewing tests E:I ratio (0.62), 30:15 ratio (0.76) and blood pressure change on standing (0.55). Using a cut-off value of 35%, risk-score sensitivity and specificity were 88 and 54%, respectively. Conclusion SUDOSCAN, which allows quick quantitative assessment of sudomotor function, may be used for early screening of CAN in everyday clinical practice before resorting to the more sophisticated and specific, but ultimately more time-consuming, Ewing tests.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Introduction La mesure de la fonction sudorale est utilisée pour évaluer l'atteinte des petites fibres du système nerveux autonome notamment chez les patients diabétiques. Le but de cette étude était ...d'évaluer la reproductibilité et la répétabilité de Sudoscan une méthode de mesure quantitative de la fonction sudorale. Patients et Méthodes Six mesures (3 appareils différents pour la reproductibilité, 2 mesures sur chaque appareil pour la répétabilité) ont été effectuées chez 18 sujets sains et 14 patients diabétiques de type 2. Pour chaque mesure, réalisée dans les conditions habituelles d'utilisation, il a été demandé au sujet se tenant debout d'appliquer la paume des mains et la plante des pieds sur de larges électrodes en inox durant 3 minutes. Les résultats disponibles immédiatement sont présentés sous forme de Conductances Cutanées Électrochimiques (CCE). Les coefficients de variations ont été calculés selon la norme iso 5725-2 sur l'exactitude des méthodes de mesures. Résultats Les données démographiques des volontaires sains étaient : 72 % d'hommes, âge : 37 ± 13 ans, IMC : 26 ± 4 kg/m2 et pour les patients diabétiques : 93 % d'hommes, âge : 62 ± 9 ans, IMC : 29 ± 5 kg/m2 . Chez les sujets sains les coefficients moyens de variations pour la répétabilité et la reproductibilité des CCE des pieds étaient respectivement de 2,8 ± 1,6 % et de 3,1 ± 1,5 % alors qu'ils étaient de 6,9 ± 6,3 % et de 6,9 ± 6,3 % chez les patients diabétiques. Pour les mains, les coefficients moyens de variations pour la répétabilité et la reproductibilité des CCE étaient respectivement de 4,2 ± 2,7 % et de 4,3 ± 2,7 % chez les sujets sains alors qu'ils étaient de 7,1 ± 5,9 % et de 7,4 ± 6,1 % chez les patients diabétiques. Discussions La plus grande variabilité observée pour les mesures des CCE des mains peut s'expliquer par la qualité de leur appui sur les électrodes qui varie moins pour les pieds. Cette étude montre une bonne reproductibilité et répétabilité des mesures réalisées avec SUDOSCAN confirmant son utilisation potentielle pour le suivi des patients et dans des études multicentriques
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
Abstract Aims The GERODIAB study is the first French multicentre, prospective, observational study that aims, through a 5-year cohort follow-up, to evaluate the link between glycaemic control and ...morbidity/mortality of type 2 diabetic (T2D) patients aged 70 years and older. This first report describes the study population at inclusion. Patients and methods A total of 987 T2D autonomous patients, aged ≥ 70 years, were recruited between June 2009 and July 2010 at 56 investigator centres. Their general parameters, diabetes characteristics and standard geriatric parameters were recorded. Results The patients’ mean age was 77 ± 5 years, with 65.2% aged 75 years or more. The mean BMI was close to 30 kg/m2 . Hypertension was found in 89.7% of patients, and 85.0% had at least one cholesterol abnormality. The mean duration of the diabetes was around 18 years, and the mean HbA1c level was about 7.5%. During the previous six months, 33.6% of patients had experienced one or several hypoglycaemias. Also, 26% of patients presented with diabetic retinopathy, 37.3% had a GFR < 60 mL/min, 31.2% had coronary insufficiency, 10.1% had heart failure, 15.8% had cerebrovascular involvement and 25.6% had peripheral vascular disease of the lower extremities. In addition, 30.5% of patients had orthostatic hypotension, 12.4% had malnutrition and 28.8% had cognitive impairment, all of which were often diagnosed at inclusion. Three-quarters of patients were taking an oral antidiabetic drug and nearly six in every 10 patients were using insulin. Conclusion This population can be considered representative of elderly, autonomous T2D patients, and its follow-up should clarify the link between glycaemic control and mortality/morbidity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
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