Chronic-diabetes-related complications simultaneously compromise both the micro- and macrovascular trees, with target organs considered as the paradigm of large vessel injury also entailing ...microangiopathic changes. However, complications independent or partially independent from vascular damage are often overlooked. This includes neuronal dysfunction (e.g., retinal neurodegeneration), interstitial injury (e.g., tubulointerstitial disease), metabolic damage (e.g., in the heart and liver), and nonclassical conditions such as cognitive decline, impaired pulmonary function, or increased risk of cancer. In this scenario, researchers, endocrinologists and primary care physicians should have a holistic view of the disease and pay further attention to all organs and all potential clinical repercussions, which would certainly contribute to a more rational and integrated patient health care.
Diabetes complications include pathological changes beyond the vascular system and classical target organs.Microangiopathy may affect nonclassical target organs.Organs affected by microangiopathy may also show neuronal or structural deficits including: neurodegeneration and neurodysfunction of the retina; structural changes in the kidney tubular interstitium; and nerve fiber dysfunction.Organs affected by macroangiopathy also show microvascular and neuronal deficits including: microangiopathy of the arterial wall; microangiopathy and neuropathic changes adding to ischemic and nonischemic heart disease; metabolic peripheral nerve damage; cerebral small vessel disease; and structural changes leading to cognitive impairment.Nonclassical chronic complications include abnormal pulmonary function and microangiopathy, metabolic liver and myocardial damage, and increased risk of carcinogenesis.
Aims
To evaluate short‐ and long‐term glycaemic control and hypoglycaemia incidence in insulin‐naïve patients ≥30 years of age with type 2 diabetes (T2DM) initiating basal insulin (BI) with or ...without oral anti‐hyperglycaemic drugs (OADs).
Methods
This was an observational, retrospective longitudinal analysis of electronic medical records from 5 European countries and the USA. A multivariable logistic regression model assessed baseline and short‐term (0‐3 months post BI initiation) factors associated with long‐term (3‐24 months) glycaemic control and hypoglycaemia.
Results
Overall, 40 627 patients were included; 20.9% and 27.8% achieved the general HbA1c target of ≤7% at 3 and 24 months post BI initiation, respectively. Failure to achieve HbA1c ≤7% at 3 months was associated with increased risk of failing to achieve target at 24 months (odds ratio OR, 3.70 95% CI, 3.41‐4.00). Over 24 months, 8.9% of patients experienced a recorded hypoglycaemic event. Hypoglycaemia during the initial 3‐month period was associated with longer‐term risk of these events over the ensuing 3 to 24 months (OR, 5.71 95% CI, 4.67‐6.99).
Conclusions
Initiating BI with or without OADs is associated with short‐ and long‐term suboptimal glycaemic control; the majority of patients fail to achieve HbA1c target ≤7% in the first 3 months, or after 2 years of BI treatment. Treatment response and hypoglycaemia incidence by 3 months post BI initiation are associated with longer‐term glycaemic control and hypoglycaemic risk, respectively. These results support the need for early anti‐hyperglycaemic interventions that more effectively control blood glucose levels without increasing the risk of hypoglycaemia.
Cardiovascular diseases (CVDs) are the main cause of death among patients with type 2 diabetes mellitus (T2DM), particularly in low- and middle-income countries. To effectively prevent the ...development of CVDs in T2DM, considerable effort has been made to explore novel preventive approaches, individualized glycemic control and cardiovascular risk management (strict blood pressure and lipid control), together with recently developed glucose-lowering agents and lipid-lowering drugs. This review mainly addresses the important issues affecting the choice of antidiabetic agents and lipid, blood pressure and antiplatelet treatments considering the cardiovascular status of the patient. Finally, we also discuss the changes in therapy principles underlying CVDs in T2DM.
The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether diet, physical activity or both can prevent or delay T2DM and ...its associated complications in at-risk people is unknown.
To assess the effects of diet, physical activity or both on the prevention or delay of T2DM and its associated complications in people at increased risk of developing T2DM.
This is an update of the Cochrane Review published in 2008. We searched the CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, ICTRP Search Portal and reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was January 2017. We continuously used a MEDLINE email alert service to identify newly published studies using the same search strategy as described for MEDLINE up to September 2017.
We included randomised controlled trials (RCTs) with a duration of two years or more.
We used standard Cochrane methodology for data collection and analysis. We assessed the overall quality of the evidence using GRADE.
We included 12 RCTs randomising 5238 people. One trial contributed 41% of all participants. The duration of the interventions varied from two to six years. We judged none of the included trials at low risk of bias for all 'Risk of bias' domains.Eleven trials compared diet plus physical activity with standard or no treatment. Nine RCTs included participants with impaired glucose tolerance (IGT), one RCT included participants with IGT, impaired fasting blood glucose (IFG) or both, and one RCT included people with fasting glucose levels between 5.3 to 6.9 mmol/L. A total of 12 deaths occurred in 2049 participants in the diet plus physical activity groups compared with 10 in 2050 participants in the comparator groups (RR 1.12, 95% CI 0.50 to 2.50; 95% prediction interval 0.44 to 2.88; 4099 participants, 10 trials; very low-quality evidence). The definition of T2DM incidence varied among the included trials. Altogether 315 of 2122 diet plus physical activity participants (14.8%) developed T2DM compared with 614 of 2389 comparator participants (25.7%) (RR 0.57, 95% CI 0.50 to 0.64; 95% prediction interval 0.50 to 0.65; 4511 participants, 11 trials; moderate-quality evidence). Two trials reported serious adverse events. In one trial no adverse events occurred. In the other trial one of 51 diet plus physical activity participants compared with none of 51 comparator participants experienced a serious adverse event (low-quality evidence). Cardiovascular mortality was rarely reported (four of 1626 diet plus physical activity participants and four of 1637 comparator participants (the RR ranged between 0.94 and 3.16; 3263 participants, 7 trials; very low-quality evidence). Only one trial reported that no non-fatal myocardial infarction or non-fatal stroke had occurred (low-quality evidence). Two trials reported that none of the participants had experienced hypoglycaemia. One trial investigated health-related quality of life in 2144 participants and noted that a minimal important difference between intervention groups was not reached (very low-quality evidence). Three trials evaluated costs of the interventions in 2755 participants. The largest trial of these reported an analysis of costs from the health system perspective and society perspective reflecting USD 31,500 and USD 51,600 per quality-adjusted life year (QALY) with diet plus physical activity, respectively (low-quality evidence). There were no data on blindness or end-stage renal disease.One trial compared a diet-only intervention with a physical-activity intervention or standard treatment. The participants had IGT. Three of 130 participants in the diet group compared with none of the 141 participants in the physical activity group died (very low-quality evidence). None of the participants died because of cardiovascular disease (very low-quality evidence). Altogether 57 of 130 diet participants (43.8%) compared with 58 of 141 physical activity participants (41.1%) group developed T2DM (very low-quality evidence). No adverse events were recorded (very low-quality evidence). There were no data on non-fatal myocardial infarction, non-fatal stroke, blindness, end-stage renal disease, health-related quality of life or socioeconomic effects.Two trials compared physical activity with standard treatment in 397 participants. One trial included participants with IGT, the other trial included participants with IGT, IFG or both. One trial reported that none of the 141 physical activity participants compared with three of 133 control participants died. The other trial reported that three of 84 physical activity participants and one of 39 control participants died (very low-quality evidence). In one trial T2DM developed in 58 of 141 physical activity participants (41.1%) compared with 90 of 133 control participants (67.7%). In the other trial 10 of 84 physical activity participants (11.9%) compared with seven of 39 control participants (18%) developed T2DM (very low-quality evidence). Serious adverse events were rarely reported (one trial noted no events, one trial described events in three of 66 physical activity participants compared with one of 39 control participants - very low-quality evidence). Only one trial reported on cardiovascular mortality (none of 274 participants died - very low-quality evidence). Non-fatal myocardial infarction or stroke were rarely observed in the one trial randomising 123 participants (very low-quality evidence). One trial reported that none of the participants in the trial experienced hypoglycaemia. One trial investigating health-related quality of life in 123 participants showed no substantial differences between intervention groups (very low-quality evidence). There were no data on blindness or socioeconomic effects.
There is no firm evidence that diet alone or physical activity alone compared to standard treatment influences the risk of T2DM and especially its associated complications in people at increased risk of developing T2DM. However, diet plus physical activity reduces or delays the incidence of T2DM in people with IGT. Data are lacking for the effect of diet plus physical activity for people with intermediate hyperglycaemia defined by other glycaemic variables. Most RCTs did not investigate patient-important outcomes.
Randomised controlled trials and other prospective clinical studies for novel medical interventions in people with diabetes have traditionally reported HbA
as the measure of average blood glucose ...levels for the 3 months preceding the HbA
test date. The use of this measure highlights the long-established correlation between HbA
and relative risk of diabetes complications; the change in the measure, before and after the therapeutic intervention, is used by regulators for the approval of medications for diabetes. However, with the increasing use of continuous glucose monitoring (CGM) in clinical practice, prospective clinical studies are also increasingly using CGM devices to collect data and evaluate glucose profiles among study participants, complementing HbA
findings, and further assess the effects of therapeutic interventions on HbA
. Data is collected by CGM devices at 1-5 min intervals, which obtains data on glycaemic excursions and periods of asymptomatic hypoglycaemia or hyperglycaemia (ie, details of glycaemic control that are not provided by HbA
concentrations alone that are measured continuously and can be analysed in daily, weekly, or monthly timeframes). These CGM-derived metrics are the subject of standardised, internationally agreed reporting formats and should, therefore, be considered for use in all clinical studies in diabetes. The purpose of this consensus statement is to recommend the ways CGM data might be used in prospective clinical studies, either as a specified study endpoint or as supportive complementary glucose metrics, to provide clinical information that can be considered by investigators, regulators, companies, clinicians, and individuals with diabetes who are stakeholders in trial outcomes. In this consensus statement, we provide recommendations on how to optimise CGM-derived glucose data collection in clinical studies, including the specific glucose metrics and specific glucose metrics that should be evaluated. These recommendations have been endorsed by the American Association of Clinical Endocrinologists, the American Diabetes Association, the Association of Diabetes Care and Education Specialists, DiabetesIndia, the European Association for the Study of Diabetes, the International Society for Pediatric and Adolescent Diabetes, the Japanese Diabetes Society, and the Juvenile Diabetes Research Foundation. A standardised approach to CGM data collection and reporting in clinical trials will encourage the use of these metrics and enhance the interpretability of CGM data, which could provide useful information other than HbA
for informing therapeutic and treatment decisions, particularly related to hypoglycaemia, postprandial hyperglycaemia, and glucose variability.
Achieving target glycaemic control is essential in people with diabetes to minimize the risk of long‐term complications, and many people with type 2 diabetes will ultimately require basal insulin ...(BI) therapy to achieve their individualized glycaemic targets. Usually, the first 12 weeks following initiation of BI therapy represents the period when the greatest dose increases and glycaemic reductions occur. Effective glycaemic control combined with minimizing the risk of hypoglycaemia is important to enable the achievement of glycaemic control in the longer term. However, substantial therapeutic inertia exists in clinical practice, both in initiation and up‐titration of BI, owing to patient‐, physician‐ and healthcare system‐related barriers, including fear of hypoglycaemia and the perception of a burdensome regimen. The more prolonged duration of action, reduced glycaemic variability and lower risk of hypoglycaemia seen with second‐generation versus first‐generation BI analogues may help alleviate patients’ and physicians’ concerns and facilitate titration. In turn, optimal BI titration and subsequent metabolic benefits may help improve therapy adherence and self‐management. This review details the clinical implications of prompt titration of BI to achieve early glycaemic control, and the importance of minimizing hypoglycaemia risk within the initial titration period. Facilitation of patients’ self‐management of BI is also addressed.
ObjectivesTo evaluate the prevalence and coprevalence of several chronic conditions in patients with type 2 diabetes in a Mediterranean region.DesignA cross-sectional study.SettingTwo hundred and ...eighty-six primary care teams of the Catalonian Health Institute (Catalonia, Spain).ParticipantsWe included patients aged ≥18 years with a diagnosis of type 2 diabetes by 31 December, 2016, who were registered in the Information System for the Development of Research in primary care (SIDIAP) database. We excluded patients with a diagnosis of type 1 diabetes, gestational diabetes mellitus and any other type of diabetes.Primary and secondary outcome measuresWe collected data on diabetes-related comorbidities (ie, chronic complications, associated cardiovascular risk factors and treatment complications). Diagnoses were based on the International Classification of Diseases, 10th Revision codes recorded in the database or, for some entities, on the cut-off points for a particular test result or a specific treatment indicated for that entity. The presence and stage of chronic kidney disease (CKD) were based on the glomerular filtration rate, the CKD Epidemiology Collaboration creatinine equation and the urine albumin-to-creatinine ratio.ResultsA total of 373 185 patients were analysed. 82% of patients exhibited ≥2 comorbidities and 31% exhibited ≥4 comorbidities. The most frequent comorbidities were hypertension (72%), hyperlipidaemia (60%), obesity (45%), CKD (33%), chronic renal failure (CRF)(28%) and cardiovascular disease (23%). The most frequently coprevalent pairs of chronic conditions were the combination of hypertension with hyperlipidaemia (45%), obesity (35%), CKD (28%), CRF (25%) or cardiovascular disease (19%), as well as the combination of hyperlipidaemia with obesity (28%), CKD (21%), CRF (18%) or cardiovascular disease (15%); other common pairs of comorbidities were obesity/CKD, obesity/CRF, hypertension/retinopathy, hypertension/albuminuria, hypertension/urinary tract infection, CVD/CRF and CVD/CKD, which were each present in more than 10% of patients.ConclusionPatients with type 2 diabetes have a high frequency of coprevalence of metabolic risk factors, cardiovascular disease and CKD and thus require an integrated management approach.
Diabetes microangiopathy, a hallmark complication of diabetes, is characterised by structural and functional abnormalities within the intricate network of microvessels beyond well-known and ...documented target organs, i.e., the retina, kidney, and peripheral nerves. Indeed, an intact microvascular bed is crucial for preserving each organ's specific functions and achieving physiological balance to meet their respective metabolic demands. Therefore, diabetes-related microvascular dysfunction leads to widespread multiorgan consequences in still-overlooked non-traditional target organs such as the brain, the lung, the bone tissue, the skin, the arterial wall, the heart, or the musculoskeletal system. All these organs are vulnerable to the physiopathological mechanisms that cause microvascular damage in diabetes (i.e., hyperglycaemia-induced oxidative stress, inflammation, and endothelial dysfunction) and collectively contribute to abnormalities in the microvessels' structure and function, compromising blood flow and tissue perfusion. However, the microcirculatory networks differ between organs due to variations in haemodynamic, vascular architecture, and affected cells, resulting in a spectrum of clinical presentations. The aim of this review is to focus on the multifaceted nature of microvascular impairment in diabetes through available evidence of specific consequences in often overlooked organs. A better understanding of diabetes microangiopathy in non-target organs provides a broader perspective on the systemic nature of the disease, underscoring the importance of recognising the comprehensive range of complications beyond the classic target sites.
Latent autoimmune diabetes in adults (LADA) is still a poorly characterized entity. However, its prevalence may be higher than that of classical type 1 diabetes. Patients with LADA are often ...misclassified as type 2 diabetes. The underlying autoimmune process against β-cell has important consequences for the prognosis, comorbidities, treatment choices and even patient-reported outcomes with this diabetes subtype. However, there is still an important gap of knowledge in many areas of clinical relevance. We are herein focusing on the state of knowledge of relevant clinical issues than may help in the diagnosis and management of subjects with LADA.
PDF
