Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)

XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

BACKGROUND: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain. METHODS: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less. Primary end points were composites of major macrovascular events (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke) and major microvascular events (new or worsening nephropathy or retinopathy), assessed both jointly and separately. RESULTS: After a median of 5 years of follow-up, the mean glycated hemoglobin level was lower in the intensive-control group (6.5%) than in the standard-control group (7.3%). Intensive control reduced the incidence of combined major macrovascular and microvascular events (18.1%, vs. 20.0% with standard control; hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P=0.01), as well as that of major microvascular events (9.4% vs. 10.9%; hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), primarily because of a reduction in the incidence of nephropathy (4.1% vs. 5.2%; hazard ratio, 0.79; 95% CI, 0.66 to 0.93; P=0.006), with no significant effect on retinopathy (P=0.50). There were no significant effects of the type of glucose control on major macrovascular events (hazard ratio with intensive control, 0.94; 95% CI, 0.84 to 1.06; P=0.32), death from cardiovascular causes (hazard ratio with intensive control, 0.88; 95% CI, 0.74 to 1.04; P=0.12), or death from any cause (hazard ratio with intensive control, 0.93; 95% CI, 0.83 to 1.06; P=0.28). Severe hypoglycemia, although uncommon, was more common in the intensive-control group (2.7%, vs. 1.5% in the standard-control group; hazard ratio, 1.86; 95% CI, 1.42 to 2.40; P<0.001). CONCLUSIONS: A strategy of intensive glucose control, involving gliclazide (modified release) and other drugs as required, that lowered the glycated hemoglobin value to 6.5% yielded a 10% relative reduction in the combined outcome of major macrovascular and microvascular events, primarily as a consequence of a 21% relative reduction in nephropathy. (ClinicalTrials.gov number, NCT00145925.)

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Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.

Changes in human behaviour and lifestyle over the last century have resulted in a dramatic increase in the incidence of diabetes worldwide. The epidemic is chiefly of type 2 diabetes and also the associated conditions known as 'diabesity' and 'metabolic syndrome'. In conjunction with genetic susceptibility, particularly in certain ethnic groups, type 2 diabetes is brought on by environmental and behavioural factors such as a sedentary lifestyle, overly rich nutrition and obesity. The prevention of diabetes and control of its micro- and macrovascular complications will require an integrated, international approach if we are to see significant reduction in the huge premature morbidity and mortality it causes.

Global and societal implications of the diabetes epidemic

D iabetes mellitus is a chronic illness that requires continuing medical care and ongoing patient self-management education and support to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payers, and other interested individuals with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. Specifically titled sections of the standards address children with diabetes, pregnant women, and people with prediabetes. These standards are not intended to preclude clinical judgment or more extensive evaluation and management of the patient by other specialists as needed. For more detailed information about management of diabetes, refer to references 1–3. The recommendations included are screening, diagnostic, and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A large number of these interventions have been shown to be cost-effective (4). A grading system (Table 1), developed by the American Diabetes Association (ADA) andmodeled after existingmethods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E. These standards of care are revised annually by the ADA’s multidisciplinary Professional Practice Committee, incorporating new evidence. For the current revision, committee members systematically searched Medline for human studies related to each subsection and published since 1 January 2010. Recommendations (bulleted at the beginning of each subsection and also listed in the “Executive Summary: Standards of Medical Care in Diabetesd2012”) were revised based on new evidence or, in some cases, to clarify the prior recommendation or match the strength of the wording to the strength of the evidence. A table linking the changes in recommendations to new evidence can be reviewed at http:// professional.diabetes.org/CPR_Search. aspx. Subsequently, as is the case for all Position Statements, the standards of care were reviewed and approved by the ExecutiveCommittee of ADA’s Board ofDirectors, which includes health care professionals, scientists, and lay people. Feedback from the larger clinical community was valuable for the 2012 revision of the standards. Readers who wish to comment on the “Standards of Medical Care in Diabetesd2012” are invited to do so at http://professional.diabetes.org/ CPR_Search.aspx. Members of the Professional Practice Committee disclose all potential financial conflicts of interest with industry. These disclosures were discussed at the onset of the standards revisionmeeting. Members of the committee, their employer, and their disclosed conflicts of interest are listed in the “Professional PracticeCommitteeMembers” table (see pg. S109). The AmericanDiabetes Association funds development of the standards and all its position statements out of its general revenues and does not utilize industry support for these purposes.

https://www.science-open.com/document_file/bb04d9d0-b3df-4133-9494-e71e300f4279/PubMedCentral/bb04d9d0-b3df-4133-9494-e71e300f4279.pdf

Standards of Medical Care in Diabetes—2012

Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study.

Clinical features of capsular glaucoma during a recent 15-year period were compared with those of primary open-angle glaucoma (POAG). Out of 1623 new glaucoma patients, 263 patients (16.2%) were capsular glaucoma and 268 (16.5%) were POAG. The patients with capsular glaucoma were older than the patients with POAG. The former had higher intraocular pressure, lower visual acuity, more advanced visual field change and heavier trabecular pigmentation than POAG patients at the time of initial examination. These findings suggest that capsular glaucoma is more difficult to manage than POAG and that the prognosis is poorer than for POAG. Pseudoexfoliative material was found on the pupillary border in 98.3%, on the central lens surface in 46.1%, and on the peripheral lens surface in 72.3%. Though 190 of 263 patients with capsular glaucoma (73.9%) were unilateral cases, 38.9% of the fellow eyes had some abnormalities related to glaucoma. Phakodonesis was found in 10% of patients with capsular glaucoma. This finding suggests that the presence of capsular glaucoma might be a risk factor in cataract surgery.

Clinical features of capsular glaucoma in comparison with primary open-angle glaucoma in Japan.

The choroid of primates possesses an elaborate nitrergic nerve fiber plexus containing a great number of ganglion cells. Postganglionic nerve fibers innervate mainly the choroidal vasculature. In addition, the choroid contains an elastic muscular system closely associated to the vasculature. The goal of the present investigation was to analyze how sustained IOP elevation would affect the choroidal vasculature with its specialized innervation and the adjacent retina. For this purpose the posterior eye segment of 15 rhesus monkeys which after laser coagulation of the trabecular meshwork developed elevated IOP up to 4 years were studied using immunohistochemical and histochemical methods, and scanning electron microscopy of corrosion casts. The most striking finding was a significant reduction of choroidal thickness and loss of choroidal ganglion cells and nerve fibers, especially in the central portion of the choroid. Corrosion casts of the choroidal vasculature showed a slight decrease in capillary density and a decrease in length of the arterioles in glaucomatous eyes. Whole mount preparations of the retina stained for NADPH diaphorase revealed a significant reduction in positively stained amacrine cells, reduction in diameter of arterioles and changes in the staining pattern of the retinal vasculature, particularly in the perimacular region.

Choroidal ganglion cell plexus and retinal vasculature in monkeys with laser-induced glaucoma.

Trabeculectomy specimens from 11 patients with juvenile glaucoma were studied by electron microscopy and quantitatively evaluated. In all cases, large amounts of extracellular material arranged in a fingerprint-like pattern, resembling basement-membrane-like material (FBM) was found, similar to that described in steroid-induced glaucoma. This material was found mainly within the inner cribriform and outer corneoscleral regions of the trabecular meshwork, and caused the cribriform layer to be greatly thickened. FBM was also intimately associated with trabecular cells, which frequently appeared activated. In 3 cases, there was also an increase in fine fibrillar material which resembled that found in eyes with steroid-induced glaucoma. The amount of sheath-derived plaque material, which is increased in primary open angle glaucoma, was greatly increased in the subendothelial layer adjacent to Schlemm's canal.

Ultrastructural changes in the trabecular meshwork of juvenile glaucoma.

Disturbances of accommodation are part of the spectrum of neuro-ophthalmological findings in patients with Minamata disease. The authors conducted a study in an animal model of mercury toxicity to identify the anatomical lesions underlying these defects. Three common marmosets received 1.0 mg/kg of methylmercury chloride (MMC) twice weekly for seven to ten weeks until signs of mercury toxicity evolved. Histopathological analysis revealed severe neuronal loss and proliferation of astroglia in the Edinger-Westphal (EW) and anteromedian (AM) nuclei of the midbrain. Less severe neuronal degeneration was observed in the cerebral cortex surrounding the lateral sulcus. In addition, a single animal showed gliosis in the region of the fastigial nucleus of the cerebellum. Among cortical and subcortical structures involved in accommodation the EW and AM nuclei were the most severely affected.The authors' results suggest that impaired accommodation in patients with methylmercury intoxication arises mainly from lesion...

Naohiko Furuyoshi

Papers

Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study.

Clinical features of capsular glaucoma in comparison with primary open-angle glaucoma in Japan.

Choroidal ganglion cell plexus and retinal vasculature in monkeys with laser-induced glaucoma.

Ultrastructural changes in the trabecular meshwork of juvenile glaucoma.

Disturbances of accommodation in Minamata disease: A neuropathological study of methylmercury toxicity in common marmoset monkeys