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Diabetes, bone and glucose-lowering agents: basic biology.

ABSTRACT: Skeletal fragility often accompanies diabetes and does not appear to correlate with low bone mass or trauma severity in individuals with diabetes. Instead (and in contrast to those with osteoporotic bone disease), bone remodelling and bone turnover are compromised in both type 1 and type 2 diabetes, contributing to defective bone material quality. This review is one of a pair discussing the relationship between diabetes, bone and glucose-lowering agents; an accompanying review is provided in this issue of Diabetologia by Ann Schwartz (DOI: 10.1007/s00125-017-4283-6 ). This review presents basic science evidence that, alongside other organs, bone is affected in diabetes via impairments in glucose metabolism, toxic effects of glucose oxidative derivatives (advance glycation end-products [AGEs]), and via impairments in bone microvascular function and muscle endocrine function. The cellular and molecular basis for the effects of diabetes on bone are discussed, as is the impact of diabetes on the stem cell niche and fracture healing. Furthermore, the safety of clinically approved glucose-lowering therapies and the possibility of developing a single therapy that would be beneficial for both insulin sensitisation and diabetes bone syndrome are outlined.

SUBMITTER: Lecka-Czernik B

PROVIDER: S-EPMC5487688 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Diabetes, bone and glucose-lowering agents: basic biology.

Lecka-Czernik Beata B

Diabetologia 20170422 7

Skeletal fragility often accompanies diabetes and does not appear to correlate with low bone mass or trauma severity in individuals with diabetes. Instead (and in contrast to those with osteoporotic bone disease), bone remodelling and bone turnover are compromised in both type 1 and type 2 diabetes, contributing to defective bone material quality. This review is one of a pair discussing the relationship between diabetes, bone and glucose-lowering agents; an accompanying review is provided in thi ...[more]

PMID: 28434032

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Project description:IntroductionMost adults with type 2 diabetes (T2D) have several chronic conditions treated with complex regimens and multiple medications. The burden and complexity of multiple medication use are associated with worse patient outcomes, including reduced adherence and increased costs, hospitalizations, mortality rates, and HbA1c. This study quantifies the chronic medication burden, regimen complexity, and potential medication interactions in patients with T2D using a nationwide claims database in the USA.MethodsAdults with T2D treated for greater than half of the year with at least one glucose-lowering agent (GLA) in 2017 were included in this descriptive study. Chronic medications were defined as all GLAs and non-GLA medications prescribed for at least 90 days in 2017 to at least 2% of the cohort. Medication burden, defined as the number of medications prescribed, was examined. Medication complexity, proxied by the Medication Regimen Complexity Index (MRCI), and potential use of interacting medications were also examined. Results were investigated for all chronic medications and were reported on the basis of the disease treated (diabetes or other condition) and the route of administration (oral or other).ResultsOn average, in 2017, the 814,156 patients included in the study filled prescriptions for 4.1 chronic medications (standard deviation [SD]?=?2.0), 3.7 oral chronic medications (SD?=?1.9), 1.5 GLAs (SD?=?0.8), and 1.1 oral GLAs (SD?=?0.7). The average MRCI was 14.7 for all chronic medications (SD?=?7.4), with a mean of 12.4 for all oral chronic medications (SD?=?6.3), 6.6 for all GLAs (SD?=?3.8), and 4.9 for oral GLAs (SD?=?2.6).ConclusionOn average, patients with T2D used multiple medications, had a complex medication regimen, and were at potential risk of medication interactions. These findings suggest that patients, practitioners, pharmacists, and payers may benefit from interventions which decrease medication burden, complexity, and/or adverse events related to the treatment of T2D.

Project description:IntroductionResearch has shown that glycemic control is associated with lower rates of microvascular and long-term cardiovascular complications. In the analyses reported here, we examined treatment failure on oral glucose-lowering agents (GLAs), defined as having sustained hemoglobin A1c (HbA1c) ≥ 7%.MethodsThis study utilized the IBM® MarketScan® Claims and Laboratory Data from 1 January 2012 through 30 June 2018. Adults with type 2 diabetes (T2D) were classified based upon the maximum number of classes of GLAs prescribed per day during the time period from 1 July 2012 through 31 December 2012. Patients were followed for 5.5 years in order to examine time to failure on oral GLAs, defined based upon receipt of ≥ 2 consecutive HbA1c results ≥ 7%. Multivariable analyses employing a Cox proportional hazards model were used to examine time to failure overall and based upon the number of index classes of oral GLAs prescribed. For patients who had sustained HbA1c above the threshold, multivariable analyses examined the duration of time that HbA1c remained above the threshold (i.e, glycemic burden) and whether or not an additional oral or injectable class of GLA was added to the patient treatment regimen (i.e., clinical inertia).ResultsA total of 4156 patients were included in the study, of whom 16% were identified with sustained HbA1c ≥ 7% after 365 days (1 year) and 36% after 730 days (2 years), with half of all patients having sustained HbA1c above target after 1102 days (3 years). There was a statistically significant difference in time to having sustained HbA1c above target based upon index classes of therapy, with patients treated with more GLAs being quicker to have HbA1c above target (P < 0.0001). Among those patients who were found to have sustained HbA1c ≥ 7%, the average number of days in the post-period that HbA1c remained above target was 1026 (2.8 years). Only 36% of patients with sustained HbA1c above target added a GLA to their treatment regimen and, for patients who did add such a therapy, the average duration from identification of HbA1c above target until treatment intensification was 401 days (1.1 years). Multivariable analyses revealed that, among those with sustained HbA1c ≥ 7%, treatment with more classes of oral GLAs was associated with a significantly higher glycemic burden and significantly lower odds of clinical inertia.ConclusionThese results indicate that for many patients treated with oral GLAs, glycemic control is not consistently achieved. For patients with above-target HbA1c , the results indicate a relatively large glycemic burden and clinical inertia towards treatment intensification. The findings illustrate some limitations associated with treatment of T2D with oral GLAs.

Project description:BackgroundEpidemiologic studies have shown a relationship between glycated hemoglobin levels and cardiovascular events in patients with type 2 diabetes. We investigated whether intensive therapy to target normal glycated hemoglobin levels would reduce cardiovascular events in patients with type 2 diabetes who had either established cardiovascular disease or additional cardiovascular risk factors.MethodsIn this randomized study, 10,251 patients (mean age, 62.2 years) with a median glycated hemoglobin level of 8.1% were assigned to receive intensive therapy (targeting a glycated hemoglobin level below 6.0%) or standard therapy (targeting a level from 7.0 to 7.9%). Of these patients, 38% were women, and 35% had had a previous cardiovascular event. The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The finding of higher mortality in the intensive-therapy group led to a discontinuation of intensive therapy after a mean of 3.5 years of follow-up.ResultsAt 1 year, stable median glycated hemoglobin levels of 6.4% and 7.5% were achieved in the intensive-therapy group and the standard-therapy group, respectively. During follow-up, the primary outcome occurred in 352 patients in the intensive-therapy group, as compared with 371 in the standard-therapy group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.16). At the same time, 257 patients in the intensive-therapy group died, as compared with 203 patients in the standard-therapy group (hazard ratio, 1.22; 95% CI, 1.01 to 1.46; P=0.04). Hypoglycemia requiring assistance and weight gain of more than 10 kg were more frequent in the intensive-therapy group (P<0.001).ConclusionsAs compared with standard therapy, the use of intensive therapy to target normal glycated hemoglobin levels for 3.5 years increased mortality and did not significantly reduce major cardiovascular events. These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)

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Diabetes, bone and glucose-lowering agents: basic biology.

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Diabetes, bone and glucose-lowering agents: basic biology.

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