Type 2 diabetes affects bone cells precursors and bone turnover.

BACKGROUND: Here we study the effect of type 2 diabetes (T2DM) on bone cell precursors, turnover and cytokines involved in the control of bone cell formation and activity. METHODS: We enrolled in the study 21 T2DM women and 21 non diabetic controls matched for age and body mass index (BMI). In each subject we measured bone cell precursors, Receptor Activator of Nuclear Factor κB (RANKL), Osteoprotegerin (OPG), Sclerostin (SCL) and Dickoppf-1 (DKK-1) as cytokines involved in the control of osteoblast and osteoclast formation and activity, bone density (BMD) and quality trough trabecular bone score (TBS) and bone turnover. T2DM patients and controls were compared for the analyzed variables by one way ANOVA for Gaussian ones and by Mann-Whitney or Kruskal-Wallis test for non-Gaussian variables. RESULTS: RANKL was decreased and DKK-1 increased in T2DM. Accordingly, patients with T2DM have lower bone turnover compared to controls. BMD and TBS were not significantly different from healthy controls. Bone precursor cells were more immature in T2DM. However the number of osteoclast precursors was increased and that of osteoblasts decreased. CONCLUSIONS: Patients with T2DM have more immature bone cells precursors, with increased number of osteoclasts and decreased osteoblasts, confirming low bone turnover and reduced cytokines such as RANKL and DKK-1. BMD and TBS are not significantly altered in T2DM although, in contrast with other studies, this may be due to the match of patients and controls for BMI rather than age.

Cognitive function may be a predictor of retinopathy progression in patients with type 2 diabetes.

PURPOSE: Microvascular and macrovascular complications of diabetes, such as retinopathy and nephropathy, progress over time and may be associated with cognitive decline. In this article, we aim to gain further insight into the association between cognitive function and retinopathy in type 2 diabetes. METHODS AND RESULTS: In this observational 8-year prospective study of 498 outpatients, demographic and clinical variables were monitored, along with retinopathy, depression, anxiety, and cognitive function. Baseline fundus photographs were available in 477 patients, 240 with no retinopathy, 110 with mild retinopathy, and 127 with moderate/more severe retinopathy. Of the first 2 groups, 279 patients were reevaluated after 8 years, of whom 181 still had no/mild retinopathy and 98 had progressed to more severe stages. On multivariate analysis, retinopathy progression was associated with being insulin-treated (p = 0.036), and worse cognitive function (p = 0.025) at baseline. CONCLUSIONS: Cognitive function may be an independent predictor of retinopathy progression.

Depression, anxiety and cognitive function in patients with type 2 diabetes: an 8-year prospective observational study.

AIMS: Since depression, anxiety and cognitive function may be impaired in type 2 diabetes, we investigated the relationships between clinical and socioeconomic variables and these psychological dimensions. METHODS: For an 8-year prospective observational study of 498 patients, 249 were not insulin-treated (NIT) and 249 were insulin-treated (IT). Demographic, socioeconomic and clinical data were monitored along with depression and anxiety (assessed by Zung questionnaire) and cognitive function by Mini Mental State Examination (MMSE). RESULTS: After 8 years, 131 patients remained NIT (NIT-NIT), 179 remained IT (IT-IT), 47 switched to insulin (NIT-IT), 111 were lost to follow-up and 30 were died. In all groups, HbA1c remained stable, BMI, glucose and lipid profile improved, and foot ulcers and retinopathy worsened. Mild worsening in depression and anxiety scores was observed in the IT-IT patients only. On multivariate analysis, worsening of depression was associated with female gender, disease duration and being IT-IT, and worsening of anxiety with disease duration. Decreased MMSE was associated inversely with smoking and directly with being IT-IT. CONCLUSIONS: Patients with type 2 diabetes are at relatively low risk of psycho-cognitive decline. However, being female and on long-term insulin treatment may be risk factors for psychological distress, suggesting that special attention is required for these patients.

Estimating the delay between onset and diagnosis of type 2 diabetes from the time course of retinopathy prevalence.

OBJECTIVE: By correlating known diabetes duration with the prevalence of retinopathy, more than 10 years have been estimated to lapse between the onset and diagnosis of type 2 diabetes. Such calculations, however, assumed a linear model, included stages of retinopathy not specific to diabetes, and allowed 5 years for retinopathy to occur after the onset of diabetes. We calculated the duration of undiagnosed type 2 diabetes in outpatients screened for retinopathy in a hospital-based diabetes clinic after correcting these assumptions. RESEARCH DESIGN AND METHODS: Diabetic patients (n = 12,074; 35,545 fundus examinations) were stratified into younger onset (YO; age at onset <30 years) or older onset (OO; age at onset ≥30 years), insulin treated (IT) or not IT (NIT), and with mild/more severe diabetic retinopathy (AnyDR) or moderate/more severe diabetic retinopathy (ModDR). The best-fitting equation correlating known duration among the OO-NIT group with the prevalence of ModDR was used to extrapolate time from appearance of retinopathy to diagnosis of type 2 diabetes. Time for retinopathy to develop after diabetes was calculated from the equation correlating the duration among the YO-IT group with appearance of ModDR. RESULTS: There were 1,719 patients in the OO-NIT group with AnyDR and 685 with ModDR and 756 in the YO-IT group with AnyDR and 385 with ModDR. A linear model showed ModDR appeared 2.66 years before diagnosis among those in the OO-NIT group. A quadratic model suggested that ModDR appeared 3.29 years after diagnosis among those in the YO-IT group. The resulting estimate was 6.05 years (2.66 + 3.29) between the onset and diagnosis of diabetes, compared with 13.36 years using standard criteria. CONCLUSIONS: Using best-fitting models and stratifying by glucose-lowering treatment and severity of retinopathy substantially lowers the estimated duration of undiagnosed type 2 diabetes.

Association of autoimmunity to autonomic nervous structures with nerve function in patients with type 1 diabetes: a 16-year prospective study.

OBJECTIVE We prospectively evaluated the association between autoimmunity to autonomic nervous structures and autonomic neuropathy in type 1 diabetes in relation to clinical variables. RESEARCH DESIGN AND METHODS A cohort of 112 patients with type 1 diabetes was prospectively followed from adolescence (T0) to approximately 4 (T4) and 16 (T16) years later. Standard cardiovascular (CV) tests and neurological examination were performed and related to the presence of circulating antibodies (Ab) to autonomic nervous structures detected at T0 and T4. Quality of life was assessed by a diabetes-specific questionnaire. RESULTS Sixty-six patients (59% of the cohort) were reexamined at T16 (age 31.4 ± 2 years; disease duration 23.4 ± 3.7 years). Nineteen had circulating Ab to autonomic structures. Prevalence of abnormal tests and autonomic symptoms were higher in Ab-positive (68 and 26%, respectively) than Ab-negative (32 and 4%) patients (P < 0.05). Among Ab-positive patients, the relative risk (RR) of having at least one altered CV test was 5.77 (95% CI 1.56-21.33), and an altered deep breathing (DB) test (<15 bpm) was 14.65 (2.48-86.46). Previous glycemic control was the only other predictor (RR 1.06 [1.002-1.13]/mmol/mol HbA1c increase). Presence of Ab carried over a 68% probability of developing an altered CV test; absence of Ab carried a 91% probability of not having an altered DB test and an 89% probability of not having an altered Valsalva ratio. Autonomic neuropathy was independently associated with worse quality of life. CONCLUSIONS Circulating Ab to autonomic structures are associated with the development of autonomic dysfunction in young diabetic patients independent of glycemic control.

Quality of life, impaired vision and social role in people with diabetes: a multicenter observational study.

Diabetic retinopathy may induce visual impairment. We evaluated vision-related quality of life in patients with visual acuity <5/10 in the better eye induced by retinopathy using the 25-item National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25). The NEI VFQ-25 was self-administered to 196 patients in 3 Italian centres (A, B and C; n = 64, 61 and 71, respectively) dedicated to DR screening and treatment. Patients in the 3 centres did not differ by age, gender, occupation and diabetes duration. Multivariate analysis demonstrated that reduced visual acuity was associated with decreased scores for General Vision, Near Activities, Distance Activities, Visual-Specific Social Functioning, Mental Health, Role Difficulties and Dependency, Driving, Colour Vision and Peripheral Vision (p < 0.01, all). Treatment by photocoagulation was associated with reduced scores in General Health (-8.3; p = 0.002), General Vision (-7.2; p = 0.001), Visual-Specific Role Difficulties (-8.8; p = 0.015) and Driving (-13.7; p = 0.003). Centre affiliation was associated with different scores for General Health, Ocular pain, Distance Activities, Visual-Specific Social Functioning and Role Difficulties and Peripheral Vision. Women had higher scores for General Vision (p = 0.015), Near Activities (p = 0.005), Distance Activities (p = 0.006), Visual-Specific Social Functioning (p = 0.03), Visual-Specific Mental Health (p = 0.035) and Colour Vision (p = 0.012). Diabetic retinopathy and vision loss modify the way people perceive their own ability to function autonomously. More data should be collected to confirm this interpretation and to guide the development of more appropriate settings to improve approach and support to patients.

Rethink Organization to iMprove Education and Outcomes (ROMEO): a multicenter randomized trial of lifestyle intervention by group care to manage type 2 diabetes.

OBJECTIVE: A trial was performed to establish whether our group care model for lifestyle intervention in type 2 diabetes can be exported to other clinics. RESEARCH DESIGN AND METHODS: This study was a 4-year, two-armed, multicenter controlled trial in 13 hospital-based diabetes clinics in Italy (current controlled trials no. ISRCTN19509463). A total of 815 non-insulin-treated patients aged <80 years with > or =1 year known diabetes duration were randomized to either group or individual care. RESULTS: After 4 years, patients in group care had lower A1C, total cholesterol, LDL cholesterol, triglycerides, systolic and diastolic blood pressure, BMI, and serum creatinine and higher HDL cholesterol (P < 0.001, for all) than control subjects receiving individual care, despite similar pharmacological prescriptions. Health behaviors, quality of life, and knowledge of diabetes had become better in group care patients than in control subjects (P < 0.001, for all). CONCLUSIONS: The favorable clinical, cognitive, and psychological outcomes of group care can be reproduced in different clinical settings.

A 5-year randomized controlled study of learning, problem solving ability, and quality of life modifications in people with type 2 diabetes managed by group care.

OBJECTIVE: To study time course changes in knowledge, problem solving ability, and quality of life in patients with type 2 diabetes managed by group compared with individual care and education. RESEARCH DESIGN AND METHODS: We conducted a 5-year randomized controlled clinical trial of continuing systemic education delivered by group versus individual diabetes care in a hospital-based secondary care diabetes unit. There were 120 patients with non-insulin-treated type 2 diabetes enrolled and randomly allocated to group or individual care. Eight did not start and 28 did not complete the study. The main outcome measures were knowledge of diabetes, problem solving ability, quality of life, HbA1c, BMI, and HDL cholesterol. RESULTS: Knowledge of diabetes and problem solving ability improved from year 1 with group care and worsened among control subjects (P<0.001 for both). Quality of life improved from year 2 with group care but worsened with individual care (P<0.001). HbA1c level progressively increased over 5 years among control subjects (+1.7%, 95% CI 1.1-2.2) but not group care patients (+0.1%, -0.5 to 0.4), in whom BMI decreased (-1.4, -2.0 to -0.7) and HDL cholesterol increased (+0.14 mmol/l, 0.07-0.22). CONCLUSIONS: Adults with type 2 diabetes can acquire specific knowledge and conscious behaviors if exposed to educational procedures and settings tailored to their needs. Traditional one-to-one care, although delivered according to optimized criteria, is associated with progressive deterioration of knowledge, problem solving ability, and quality of life. Better cognitive and psychosocial results are associated with more favorable clinical outcomes.