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From the Veterans Affairs Center for Practice Management and Outcomes Research and the University of Michigan School of Medicine, Ann Arbor, Michigan. Grant Support: In part by grant HSO 6665-01 from the Agency for Health Care Policy and Research. Requests for Reprints: Sandeep Vijan, MD, Veterans Affairs Health Services Research and Development, PO Box 130170, Ann Arbor, MI 48113-0170. Background: The benefits of intensive glycemic control in patients with type 2 diabetes are not well quantified.
Anyone can submit a comment any time after publication, but only those submitted within 4 weeks of an article’s publication will be considered for print publication. Our New BMJ website does not support IE6 please upgrade your browser to the latest version or use alternative browsers suggested below. Objective: To determine the relation between systolic blood pressure over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. Results: The incidence of clinical complications was significantly associated with systolic blood pressure, except for cataract extraction. Conclusions: In patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised blood pressure. People with type 2 diabetes have a greater incidence of cardiovascular disease, cerebrovascular disease, and renal disease than the general population. In these analyses, we evaluated the relation between systolic blood pressure over time and the development of macrovascular and microvascular complications using data from the UKPDS and looked for possible thresholds. We studied the incidence of complications of diabetes in the 4801 white, Asian Indian, and Afro-Caribbean patients who had blood pressure measured at two and nine months after the diagnosis of diabetes.
The UKPDS clinical trials of blood glucose and blood pressure control are described elsewhere.
Blood pressure was measured with the person in a seated position after a five minute rest with a Copal UA-251 or a Takeda UA-751 electronic, auscultatory blood pressure reading machine (Andrew Stephens, Brighouse, West Yorkshire). Blood pressure was measured firstly at baseline (mean of measures taken at two and nine months after diagnosis) and secondly as an updated mean of annual measurement of systolic blood pressure, calculated for each participant from baseline to each year of follow up. The biochemical methods used have been reported previously.21 Biochemical variables are quoted for measurements after the initial dietary run-in period.
The clinical end points studied18 and their definitions19 were separated into aggregate and single end points (see box). The unadjusted incidence rates were calculated by dividing the number of people with a given complication by the person years of follow up for the given complication within each category of updated mean systolic blood pressure and reported as events per 1000 person years of follow up.
To assess potential associations between updated mean systolic blood pressure and complications we used proportional hazards (Cox) models. The regression lines were fitted with updated mean systolic blood pressure as a continuous variable centred on the mean of the risk estimates for the categories 130–139 mm Hg and 140–149 mm Hg.
To assess whether treatment with drugs to lower blood pressure reduced the complications independently of the reduction in blood pressure, a proportional hazards model was fitted that included allocation to tight versus less tight blood pressure policies, updated mean systolic blood pressure, age, sex, ethnic group, smoking, and concentrations of high and low density lipoprotein cholesterol, triglyceride, and albuminuria. The risk of each of the macrovascular and microvascular complications of type 2 diabetes evaluated was strongly associated with blood pressure, as measured by updated mean systolic blood pressure.
Fig 3 Hazard rates (95% confidence intervals as floating absolute risks) as estimate of association between category of updated mean systolic blood pressure and any end point related to diabetes, death related to diabetes, and all cause mortality with log linear scales.
The estimated hazard ratios associated with each category of updated mean systolic blood pressure, relative to the lowest category, are shown as log linear plots in figures 3 and 4. Fig 4 Hazard rates (95% confidence intervals as floating absolute risks) as estimate of association between category of updated mean systolic blood pressure and myocardial infarction, stroke, microvascular end points, cataract extraction, lower extremity amputation, or fatal peripheral vascular disease and heart failure, with log linear scales. There was no indication of a threshold for any of the complications examined below which risk no longer decreased nor a level above which risk no longer increased. This observational analysis shows an important association between the occurrence of each of the diabetic complications evaluated (except cataract extraction), including all cause mortality, and systolic blood pressure exposure across the range observed in patients with type 2 diabetes. This observational analysis provides an estimate of the reduction in risk that might be achieved by the therapeutic lowering of blood pressure.
According to the NHS an estimated two million women in the UK suffer from endometriosis while one in 10 are expected to experience symptoms in their lifetime.
Vijan, Hofer, and Hayward: Veterans Affairs Health Services Research and Development, PO Box 130170, Ann Arbor, MI 48113-0170.


Each node was encountered yearly, and the probabilities of remaining at the same level, advancing to the next complication, or dying were encountered.
One month after publication, editors review all posted comments and select some for publication in the Letters section of the print version of Annals. Secondary aggregate outcomes: myocardial infarction, stroke, lower extremity amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photocoagulation). Any reduction in blood pressure is likely to reduce the risk of complications, with the lowest risk being in those with systolic blood pressure less than 120 mm Hg. Complementary information for estimates of the risk of complications including myocardial infarction at different levels of blood pressure can be obtained from observational analysis of the UKPDS data. Epidemiological studies suggest that relative hyperglycaemia accounts for part but not all of the increased risk.2–7 Raised blood pressure is more common in people with type 2 diabetes than in the general population,8–12 and in people without diabetes it is a major risk factor for myocardial infarction and stroke. Recruitment occurred between 1977 and 1991 at 23 clinical centres in England, Scotland, and Northern Ireland.
Of these, 3642 with complete data for potential confounders were evaluated in proportional hazards models. The first reading was discarded, and the mean of the next three consecutive readings with a coefficient of variation below 15% was used. For example, at one year the updated mean is the average of the baseline and one year values and at three years it is the average of baseline, one year, two year, and three year values. These parameters were chosen to reflect the cohort's median age and duration of diabetes and modal ethnic group and sex. The P value reported is that associated with systolic blood pressure as a continuous variable. An interaction term between blood pressure treatment and mean updated blood pressure was included.
Incidence of complications in patients with type 2 diabetes by category of updated mean systolic blood pressure.
The updated mean systolic blood pressure showed similar risk relations to baseline systolic blood pressure (table 3).
This association persisted after adjustment for other characteristics that are associated with risk of complications (age, sex, ethnic group, glycaemia, lipid concentrations, smoking, and albuminuria). While it is important to realise that epidemiological associations cannot necessarily be transferred to clinical practice, the results are consistent with those achieved by the policy of tight control of blood pressure in the clinical trial.1 Whereas tight control did not significantly reduce the risk of myocardial infarction in the clinical trial, the effect size was commensurate with the observational analysis. Macrovascular And Microvascular Complications Of Type 2 Diabetes i hope my arteries don’t mind it The last one I had billed out at $7000.
Well public opinion has a way of lynching black men starting world diabetic diet calories calculator wars interning citizens and just generally being wrong…. Wahida you did it again and I can not wait for book 5… There are barriers to insulin treatment with multiple daily diabetes in the pregnancy injections (MDI). Not everyone who has been told she has PCOS really has it What happens in PCOS: Insulin resistance the newest piece of the puzzle What does IR do? 28 2007 — For the first time the American Diabetes Association (ADA) has come out in support of low-carbohydrate diets for people with diabetes who want to manage their weight. Insulin pump therapy (as only rapid- or short-acting insulin is used in pumps interruption of insulin delivery for any reason rapidly leads to insulin deficiency). Vijan is an Agency for Health Care Policy and Research Health Services Research Fellow, and Dr.
This information can help to estimate the expected reduction in the risk of diabetic complications from a given change in blood pressure.
13 14 Epidemiological studies of the role of blood pressure on the development of cardiovascular disease have categorised people as either hypertensive or normotensive or have measured blood pressure on a single occasion, 5 6 15–17 whereas repeated measurements of blood pressure over several years should be more informative. Exclusion criteria are presented elsewhere18; the main reasons were severe vascular disease, myocardial infarction or stroke within the year before recruitment, or major systemic illness.
At entry, the mean duration of known diabetes was 2.6 years, and the patients were older and heavier than in the whole cohort (table 1).
In participants with atrial fibrillation, examiners used a Hawksley random zero sphygmomanometer. Time of follow up was calculated from the end of the initial period of dietary treatment to the first occurrence of that complication or loss to follow up, death from another cause, or the end of the study on 30 September 1997 for those who did not have that complication. Evaluation of a threshold level of systolic blood pressure for each complication was assessed by visual inspection.
Figure 1 shows the incidence rated by category of updated mean systolic blood pressure for any end point related to diabetes adjusted for age, sex, ethnic group, and duration of diabetes. The risk of each of the complications evaluated, except cataract extraction, rose with increasing updated mean systolic blood pressure with and without adjustment for baseline variables including age, sex, ethnic group, lipid concentrations, HbA1c, smoking, and albuminuria. On average, each 10 mm Hg reduction in systolic blood pressure was associated with a 12% decrease in the risk of any end point related to diabetes and a 15% reduction in the risk of death related to diabetes.


The risk reductions in the clinical trial of tight control seemed to be greater than those anticipated from the epidemiological analyses for any complications or deaths related to diabetes, stroke, microvascular disease, and heart failure.1 After allowance for differences in blood pressure between the tight and less tight policies in the clinical trial, this apparent treatment effect, per se, was significant only for deaths related to diabetes, stroke, and heart failure.
Hofer is a Veterans Affairs Health Services Research and Development Career Development Awardee.
However, the Markov model predicts substantially greater benefit when moving from poor to moderate glycemic control than when moving from moderate to almost-normal glycemic control.
It can also help to assess whether or not thresholds in blood pressure exist below which the risk of complications is substantially reduced.
At each event time, the updated mean systolic blood pressure for a person with an event was compared with the updated mean systolic blood pressure of those who had not had an event by that time. The risk reduction from the continuous variable model associated with a 10 mm Hg reduction in observed systolic blood pressure was compared with the risk reduction seen in the UKPDS intervention trial of a tight versus a less tight policy of blood pressure control, for which no adjustment for potential confounders was required as they were balanced by the randomisation.1 The main exposure of interest for the observational analyses was updated mean systolic blood pressure regardless of the control policy or the antihypertensive treatments used. The increase in risk was monotonic, showing no evidence of a threshold, and showed a twofold increase over the range of systolic blood pressure from <120 mm Hg (median 114 mm Hg) to ?160 mm Hg (168 mm Hg). The decrease in risk for each 10 mm Hg reduction of updated mean systolic blood pressure was between 12% and 19% for both macrovascular and microvascular complications (table 3 and figures 3 and 4).
Myocardial infarction occurred more commonly than microvascular complications, but the relative risk reduction for a 10 mm Hg reduction in systolic blood pressure was similar at 11% and 13%, respectively. The absence of significant interaction suggests that treatment effect does not differ by level of blood pressure. Types of Diabetes There are three types of diabetes mellitus (as well as diabetes insipidus): type 1 type 2 and gestational diabetes. I would suggest this book to anybody who wants to learn biochemistry at a discussable level quickly. MAGNESIUM OXIDE Prepared at the 17th JECFA (1973) published in FNP 4 (1978) and in FNP 52 (1992). Targeting less than 20% of the patients at one health maintenance organization for intensified therapy may prevent more than 80% of the preventable patient-time spent blind. Such thresholds would have substantial influence on the establishment of guidelines on clinical care.
If this target was not met with maximal doses of a ? blocker or angiotensin converting enzyme inhibitor, additional agents were prescribed, including a loop diuretic, a calcium channel blocker, and a vasodilator.
For myocardial infarction and stroke, for participants who had a non-fatal event before a fatal event, the time to the first event was used.
The updated mean systolic blood pressure was included as a time dependent covariate to evaluate systolic blood pressure during follow up. The heart outcomes prevention evaluation studies (HOPE and MICRO-HOPE) that used ramipril can also be interpreted to have effects beyond those anticipated by changes in blood pressure alone. Figure 2 shows the adjusted incidence rates for myocardial infarction and microvascular end points, both being strongly associated to a similar degree with increasing blood pressure. 24 25 This suggests the possibility that treatment with angiotensin converting enzyme inhibitors 26 27 and ? blockers 28 29 may have cardioprotective effects separate from blood pressure reduction. In patients with later onset, moderate glycemic control prevents most end-stage complications caused by microvascular disease. Myocardial infarction, however, occurred about twice as frequently as microvascular end points at each level of blood pressure. These results have important implications for informing patients and allocating health care resources.
A separate model with updated mean systolic blood pressure as a continuous variable was used to determine risk reduction associated with a 10 mm Hg reduction in blood pressure. Thus the incidence of myocardial infarction increased from 18 per 1000 patient years in the group with the lowest systolic blood pressure to 33 per 1000 patient years in the group with blood pressure >160 mm Hg, with the comparable data for microvascular disease being 7 to 21 per 1000 patient years.
1 28 30 31 The diminished risk of heart failure may have reduced the risk of embolic stroke, but no direct data are available. Treating adults with septic shock with intensive insulin therapy to counter elevated blood glucose levels associated with corticsteroid therapy did not result in a reduced risk of in-hospital death compared to patients who received conventional insulin therapy main signs and symptoms of type 2 diabetes diabetes type 2 high sugar reading I was not watching the clock during this work-out (if it’s too exhausting or boring I tend to). Effects greater than anticipated have also been shown in studies in the general population, where the risk reduction in odds of stroke from pooled trials of antihypertensive drug treatment exceeded the 35-40% expected from epidemiological studies.32 It is possible that the association between blood pressure and cardiovascular disease differs in magnitude in diabetic and non-diabetic populations, which could not be tested in this study. 1 18 The risk reduction associated with a reduction of 10 mm Hg in updated mean systolic blood pressure was calculated as 100% minus the reciprocal of the hazard ratio expressed as a percentage.



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