Malgorzata Saryusz-Wolska

Mild cognitive impairment and depressive symptoms in elderly patients with diabetes: prevalence, risk factors, and comorbidity.

The aim of the study was to estimate the prevalence of mild cognitive impairment (MCI), depressive syndrome cases, and its comorbidity, and to identify predictors of these conditions. Methods. 276 diabetics elders were screened for MCI and depressive symptoms. Detailed information of history of diabetes, and data of BMI, HbA1c, and blood lipids were collected. Results. The prevalence of MCI was 31.5%, depressive syndrome was 29.7%, and MCI with coexisting depressive mood was 9.1%. The logistic regression analysis revealed that variables which increased the likelihood of having been diagnosed with MCI were: higher HbA1c level, previous CVD, hypertension, retinopathy, increased number of comorbidities, and less years of formal education. Significant predictors of having a depressive mood included female gender, single marital status, current and past smoking status, lack of physical activity, higher BMI and total cholesterol level, increased number of comorbidities, history of hypoglycemia, and insulin treatment. Factors associated with both MCI and depressive syndrome were female gender, single marital status, past smoking status, retinopathy, previous CVD or stroke, increased number of comorbidities, and insulin treatment. Conclusions. Depressive symptoms, MCI, and its comorbidity are common in elderly subjects with type 2 diabetes. Systematic screening could result in the identification of high-risk patients.

Serum Levels of Inflammatory Markers in Depressed Elderly Patients with Diabetes and Mild Cognitive Impairment

Objective The aim of the study was to determine the serum levels of CRP, IL-6 and TNF-α in elderly diabetic patients with depressive syndrome alone or with coexisting mild cognitive impairment (MCI). Methods 276 diabetics elders were screened for depressive symptoms (using Geriatric Depression Scale: GDS-30) and MCI (using the Montreal Cognitive Assessment: MoCA score). Data of HbA1c, blood lipids and inflammatory markers levels were collected. Results In all groups of patients levels of CRP, IL-6 and TNF-α were significantly higher as compared to controls. The highest level of inflammatory markers was detected in group with depressive mood and coexisting MCI, however IL-6 level didn’t significantly differ as compared to MCI group. We founded correlations between all inflammatory markers in group of patients with depressive mood and in group of subjects with depressive symptoms and coexisting MCI. GDS-30 score was correlated with levels of inflammatory markers in group with depressive mood, and with levels of CRP and TNF-α in group with depressive mood and coexisting MCI. In the group with depressive mood and coexisting MCI we founded that MoCA score was negatively correlated with CRP and TNF-α levels; and HbA1c level was positively correlated with all inflammatory markers. The univariate logistic regression models revealed that variables which increased the likelihood of having been diagnosed with MCI in depressed patients were: higher levels of HbA1c, CRP, IL-6 and TNF-α, previous CVD or stroke, increased number of co-morbidities and microvascular complications, older age, less years of formal education. The multivariable model showed that previous CVD, higher HbA1c and IL-6 levels are significant factors. Conclusions We demonstrated that the presence of depressive syndrome is associated with higher levels of inflammatory markers in elderly patients with diabetes. The presence of MCI in these depressed subjects has additive effect on levels of inflammatory mediators.

C-Reactive Protein, Advanced Glycation End Products, and Their Receptor in Type 2 Diabetic, Elderly Patients with Mild Cognitive Impairment

Objective The aim of the study was to evaluate serum levels of advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE), and C-reactive protein (CRP) in elderly patients with type 2 diabetes mellitus with and without mild cognitive impairment (MCI) and to determine the predictors (including AGEs, RAGE, and CRP levels) of having MCI in elderly patients with type 2 diabetes. Methods Two hundred seventy-six diabetics elders were screened for MCI (using the Montreal Cognitive Assessment: MoCA score). Data of biochemical parameters and biomarkers were collected. Results Serum AGEs, RAGE, and CRP levels were significantly increased in MCI patients compared to controls. In group of patients with MCI, serum RAGE level was positively correlated with AGEs level and with CRP level. RAGE, AGEs, and CRP concentrations were positively correlated with HbA1c levels and negatively correlated with MoCA score. The univariate logistic regression models revealed that variables, which increased the likelihood of diagnosis of MCI in elderly patients with type 2 diabetes were higher levels of HbA1c, RAGE, AGEs, CRP, TG, lower level of HDL cholesterol, previous CVD, HA, or use of HA drugs, hyperlipidemia, retinopathy, nephropathy, increased number of co-morbidities, older age, and less years of formal education. HA or use of HA drugs, previous CVD, higher level of RAGE and CRP, older age and less years of formal education are the factors increasing the likelihood of having MCI in elderly patients with type 2 diabetes in multivariable model. Conclusion In summary, serum AGEs, RAGE, and CRP are increased in the circulation of MCI elderly diabetic patients compared to controls. A larger population-based prospective study needs to be performed to further confirm the relationship between AGEs, RAGE, and the cognitive decline or progress to dementia.

Adiponectin, leptin and IL-1 β in elderly diabetic patients with mild cognitive impairment

The aim of the study was to determine the serum levels of adiponectin, leptin and IL-1 β in elderly diabetic patients with and without mild cognitive impairment (MCI) and to examine the associations of these markers with clinical and cognitive parameters. A biochemical evaluation was performed of 62 seniors with type 2 diabetes (T2DM) and MCI, and 132 seniors with T2DM but without MCI (controls). Serum leptin and IL-1 β levels were higher and adiponectin concentration was lower in MCI patients than controls. In MCI subjects, adiponectin level was negatively correlated with leptin, IL-1 β levels and BMI. Leptin concentration was correlated with IL-1 β level. Univariate logistic regression models revealed that the factors which increased the likelihood of diagnosis of MCI in elderly patients with T2DM were higher levels of HbA1c, leptin, IL-1 β and triglycerides, as well as lower levels of adiponectin and HDL cholesterol. Similarly, previous CVD, hypertension, hyperlipidemia, retinopathy, nephropathy, hypoglycemia, longer duration of diabetes, increased number of co-morbidities, older age, fewer years of formal education were found to be associated with MCI. The multivariable model indicated fewer years of formal education, previous CVD, hypertension, increased number of co-morbidities, higher HbA1c and IL-1 β levels and lower adiponectin level. Elderly diabetic patients with MCI have higher levels of leptin and IL-1 β and lower levels of adiponectin. Further prospective studies are needed to determine the role of these markers in the progression to dementia.

Pancreatic polypeptide secretion in diabetic patients with delayed gastric emptying and autonomic neuropathy

Measuring postprandial pancreatic polypeptide (PP) plasma concentration is a sensitive method for autonomic nervous system assessment. Delayed gastric emptying (DGE) often does not correlate clearly with cardiac autonomic neuropathy (CAN). This study was conducted to evaluate whether decreased PP secretion (PPS) accompanies DGE and CAN in diabetes. Fourteen long-standing diabetics with DGE assessed by scintigraphy (group A), 14 well-matched diabetics with normal gastric emptying (NGE) (group B), and 12 healthy controls (group C) were the study subjects. CAN and postprandial PPS at 0, 30, and 60 min after test meal ingestion were examined in all the subjects, and the area under curve of PP secretion was calculated. There was no correlation between DGE and CAN (eight diabetics with CAN in A and six in B). Basal PP values were almost the same in all the patients (mean 77.27 +/- 11.0 pg/mL). The area under curve of PP secretion values (PPAUC) after test meal ingestion were significantly higher in B (211.84 +/- 36.13 pg/mL/h; p < 0.0001) and C (233.68 +/- 23.43 pg/mL/h; p < 0.00001) than in A (147.59 +/- 31.77 pg/mL/h). Diabetics with CAN had lower PPS expressed as PPAUC than those without CAN, which was independent of gastric emptying rate (152.31 +/- 37.18 versus 207.12 +/- 39.21 pg/mL/h; p < 0.001). There were no significant differences between test meal-stimulated PPAUC in diabetics without CAN (207.12 +/- 39.21 pg/mL/h) and controls (233.68 +/- 23.43 pg/mL/h), and this was also independent of gastric emptying rate. In patients with both DGE and CAN, the PPS was completely blunt (PPAUC 124.04 +/- 5.71 versus 233.68 +/- 23.43 pg/mL/h in controls; p < 0.001). The PPS in diabetics with CAN and NGE was significantly lower than in controls (PPAUC 190.0 +/- 37.45 versus 233.68 +/- 23.43 pg/mL/h; p < 0.01). In conclusion, the PPS in diabetics with CAN was decreased significantly and independently of DGE. The PP secretion was very low in diabetics with both CAN and DGE.

Circadian Blood Pressure Variation and Antihypertensive Medication Adjustment in Normoalbuminuric Type 2 Diabetes Patients

Background/Aims: The aim of the study was to assess the effect of an antihypertensive treatment adjustment on 24-hour blood pressure variation in type 2 diabetes patients. Methods: The study group included 59 hypertensive type 2 diabetes patients subjected to a single one-step antihypertensive agent dose adjustment (increase or decrease). Ambulatory blood pressure monitoring was performed at baseline and 4–6 weeks after the treatment modification. Controls were 41 matched patients, in whom antihypertensive treatment remained unchanged. Results: At baseline, 45 (76%) study group patients and 29 (71%) controls were ‘non-dippers’; a similar number of patients in both groups converted to ‘dipping’ or vice versa: 11 (19%) from the study group and 7 (17%) controls. ‘Converters’ from the study group were significantly younger (47.5 ± 3.9 vs. 56.4 ± 12.2 years; p < 0.05) and had lower 24-hour systolic blood pressure than ‘non-converters’: 113.7 ± 7.2 vs. 127.7 ± 20.3 mm Hg (p < 0.01). Conclusion: A single one-step antihypertensive medication adjustment does not affect ‘dipping’ status in type 2 diabetes patients. However, the assessment of blood pressure variation should be made with greater caution in younger type 2 diabetes subjects with low systolic blood pressure.

Intensified glucose lowering in type 2 diabetes: time for a bolder reappraisal

To the Editor: We read with great interest the review by Yudkin et al. [1]. The authors, having carefully analysed the available data, concluded that glucose control, while being the weakest amongst the main cardiovascular risk contributors (hypertension + hyperlipidaemia + hyperglycaemia + smoking), is being paid too much attention in the CVD prevention and treatment guidelines. They explain that if it is at all effective, it may prolong life in many patients at best for a matter of days and, furthermore, this would cost a small fortune. Moreover, in the conclusions of the article the authors suggest that intensive glucose management should be used in those individuals with higher (which we understand to mean well over 8.0%) levels of HbA1c, particularly in those of advanced age and diminished life expectancy, and that the target of 6.5–7.0% should be completely abandoned. While we share the general view of the authors and praise their rigid analysis supported by pharmacoeconomic data, looking at data from recent large trials we have arrived at a different conclusion regarding target HbA1c values and the current role of intensified glucose control. In short, the results of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and Veterans Affairs Diabetes Trial (VADT) clearly show that aiming to reach a target HbA1c level of <6.5% or <7% is beneficial for those patients with diabetes who are younger and do not have a history of microand macrovascular complications [2, 3]. The ACCORD study was initially interpreted as a warning sign against lowering HbA1c to about 6.5% [2], but the recently published analysis [4] shows that the increase in the mortality rate was largely seen only in those who failed to achieve the target levels of 6.5%. Furthermore, the HbA1c level above which the risk of death rose substantially among those in the intensive treatment arm was about 7.0%, indicating that those who reached the intensive treatment target died less often than those who did not [4]. W. C. Duckworth, co-principal investigator of the VADT, announced at the American Diabetes Association meeting in June 2009: ‘We found that initiation of intensive control in the first 15 years after a diagnosis of type 2 diabetes reduced the risk of cardiovascular events, including mortality, but initiation 16–20 years after diagnosis yielded no such benefit. Further, initiation of intensive control 20 or more years after diagnosis increased the risk of cardiovascular events in the population studied in this trial’ [5]. A meta-analysis of the ACCORD study, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study, UK Prospective Diabetes Study (UKPDS) and VADT, performed by the Collaborators on Trials of Lowering Glucose (CONTROL) group, confirmed that achievement of an HbA1c level of <6.5% provides benefits L. Czupryniak (*) : E. Szymanska-Garbacz :M. Pawlowski : M. Saryusz-Wolska : J. Loba Internal Medicine and Diabetology Department, Barlicki University Hospital No. 1, Medical University of Lodz, Lodz, Poland e-mail: czupryniak@yahoo.co.uk

Plasma levels of thrombomodulin, plasminogen activator inhibitor-1 and fibrinogen in elderly, diabetic patients with depressive symptoms

BackgroundDiabetes, depression and aging have been associated with pro-inflammatory and prothrombotic state.AimThe aim of the study was to determine the plasma levels of thrombomodulin, plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in elderly diabetic patients with and without depressive symptoms and to examine factors (including thrombomodulin, PAI-1, fibrinogen levels) associated with depressive symptoms in elderly patients with type 2 diabetes (T2DM).MethodsA total of 276 T2DM elders were evaluated: 82 subjects with depressive symptoms and 194 controls. Data were collected concerning biochemical parameters and biomarkers.ResultsPlasma thrombomodulin, PAI-1 and fibrinogen were elevated in patients with depressive symptoms compared to controls. Thrombomodulin level was correlated with fibrinogen and PAI-1 levels. All parameters were correlated with the Geriatric Depression Scale-30 score. The univariate logistic regression models revealed that variables which increased the likelihood of diagnosis of depressive symptoms in elderly patients with T2DM were: female sex, smoking habit, longer duration of T2DM, hyperlipidemia, neuropathy, increased number of co-morbidities, higher BMI, and higher levels of total and LDL cholesterol, thrombomodulin, PAI-1 and fibrinogen. In addition, the multivariable analysis indicated that female sex, smoking habit, increased number of co-morbidities, higher BMI, and higher levels of LDL cholesterol and thrombomodulin are the predisposing factors for depressive symptoms.ConclusionsElderly diabetic patients with depressive symptoms have higher levels of thrombomodulin, PAI-1 and fibrinogen. Further prospective larger studies are needed to provide potential directions for the research, treatment and prevention of co-morbid depression and diabetes.

Discontinuing insulin therapy after diabetic ketoacidosis—is its cause worth considering?

We read with interest the paper by Hsin Yu et al . [1], and found it of significant practical importance. However, we believe that the authors missed an important issue in clinical characteristics of diabetic ketoacidosis (DKA), as no data on possible causes of DKA in the studied group are presented. DKA might occur in diabetes at the onset of the disease, and later on due to insulin omission or infection [2,3]. It is less clear what causes DKA in newly diagnosed subjects, who later do not require insulin to control blood glucose. We suggest that a specific cause of DKA might also be a useful predictor of insulin discontinuation in further stages of the disease. We describe a case of a patient who was diagnosed with diabetes and DKA, in whom insulin was withdrawn after 2 months. He presented with all three factors associated with insulin discontinuation described by Hsin Yu et al . [1]. On 1 February 2001, the patient (male, Caucasian, aged 53 years, body mass index 28.7 kg/m 2 ) was referred to the Metabolic Diseases Department with DKA and an upper respiratory tract infection. His personal medical history was unremarkable, although three members of the patient’s family were diabetic. In the previous 3 days he had noticed increased thirst and polyuria. He presented with features of diabetic ketotic acidosis (blood glucose 41.1 mmol/ l, pH 7.26, serum bicarbonate 9.8 mmol/ l, base excess [ − 14.9] mmol/ l), was dehydrated, tachypnoeic, and had symptoms of severe purulent pharyngitis. Other laboratory abnormalities included elevated leucocyte count (14 850/ μ l, with 83.7% of neutrophils) and significantly elevated creatinine kinase (CK) up to 50 880 IU/l (reference range 10–90 IU/l). Intravenous insulin as well as antibiotic and fluids were initiated and the patient’s general condition improved promptly. CK levels decreased to normal values within 6 days as did his blood cell count. His initial daily insulin dose was 103 IU, after 7 days it decreased to 72 IU, and at discharge, after 15 days of hospital treatment, he was taking 52 IU of insulin per day in multiple doses. His anti-GAD assay was negative. Ophthalmologic and neurological examinations were unremarkable. After hospital stay the patient’s insulin requirement was decreasing steadily, and after 6 weeks insulin therapy was discontinued. He was switched to glibenclamide 5 mg t.i.d. Nevertheless, he experienced hypoglycaemia and eventually, after 4 months, all pharmacological treatment was stopped. His mean daily blood glucose was between 4.5 and 5.0 mmol/l and his diabetes was managed by diet. The case is a good example of a person in whom insulin therapy discontinuation would be expected according to the criteria proposed by Hsin Yu et al . [1]. He was over 40 years of age at diagnosis, DKA was his first symptom of diabetes and he was overweight. However, we believe that the cause of DKA should also be taken into consideration. Severe infection is a wellknown precipitating factor of ketoacidosis in diabetic patients [2]. Our patient developed DKA following severe pharyngitis, but within weeks of its treatment no longer needed insulin. It would therefore be interesting to learn which subjects studied by Hsin Yu et al . presented with infection. This might be another factor predicting insulin discontinuation. Finally, the general conclusion drawn from the work of Hsin Yu et al . and other observations [4,5] suggests that ceasing insulin therapy is not uncommon in diabetes patients. However, more studies are needed to shed light on this somewhat understudied area of insulin therapy.

Serum Soluble Adhesion Molecules and Markers of Systemic Inflammation in Elderly Diabetic Patients with Mild Cognitive Impairment and Depressive Symptoms.

The aim of the study was to determine the serum levels of soluble adhesion molecules and hs-CRP in elderly diabetics with mild cognitive impairment (MCI) alone or with depressive symptoms. Methods. 219 diabetics elders were screened for psychiatric disorders and divided: group 1, MCI without depressive mood; group 2, MCI with depressive mood; group 3, controls. Data of biochemical parameters and biomarkers were collected. Results. In groups 1 and 2 levels of all biomarkers were significantly higher as compared to controls. The highest level of hs-CRP and sICAM-1 was detected in group 2. SVCAM-1 and sE-selectin levels were also the highest in group 2; however they did not significantly differ as compared to group 1. MoCA score was negatively correlated with all biomarkers in group 1. The logistic regression model showed that variables which increased the likelihood of having depressive syndrome in MCI patients were older age, stroke, neuropathy, increased number of comorbidities, and higher sICAM-1 level. Conclusions. We first demonstrated that elderly diabetic patients with MCI, particularly those with depressive mood have higher levels of soluble adhesion molecules and markers of low-grade systemic inflammation. Coexisting depressive syndrome in patients with MCI through common inflammatory pathways may result in augmentation of psychiatric disorders.