Matthew Knuiman

Bio: Matthew Knuiman is an academic researcher from University of Western Australia. The author has contributed to research in topics: Population & Risk factor. The author has an hindex of 76, co-authored 361 publications receiving 23067 citations. Previous affiliations of Matthew Knuiman include Royal Perth Hospital & University of Western Ontario.

Onset of NIDDM occurs at Least 4–7 yr Before Clinical Diagnosis

Abstract: Objective To investigate duration of the period between diabetes onset and its clinical diagnosis. Research Design and Methods Two population-based groups of white patients with non-insulin-dependent diabetes (NIDDM) in the United States and Australia were studied. Prevalence of retinopathy and duration of diabetes subsequent to clinical diagnosis were determined for all subjects. Weighted linear regression was used to examine the relationship between diabetes duration and prevalence of retinopathy. Results Prevalence of retinopathy at clinical diagnosis of diabetes was estimated to be 20.8% in the U.S. and 9.9% in Australia and increased linearly with longer duration of diabetes. By extrapolating this linear relationship to the time when retinopathy prevalence was estimated to be zero, onset of detectable retinopathy was calculated to have occurred ∼ 4–7 yr before diagnosis of NIDDM. Because other data indicate that diabetes may be present for 5 yr before retinopathy becomes evident, onset of NIDDM may occur 9–12 yr before its clinical diagnosis. Conclusions These findings suggest that undiagnosed NIDDM is not a benign condition. Clinically significant morbidity is present at diagnosis and for years before diagnosis. During this preclinical period, treatment is not being offered for diabetes or its specific complications, despite the fact that reduction in hyperglycemia, hypertension, and cardiovascular risk factors is believed to benefit patients. Imprecise dating of diabetes onset also obscures investigations of the etiology of NIDDM and studies of the nature and importance of risk factors for diabetes complications.

The Rising Prevalence of Diabetes and Impaired Glucose Tolerance: The Australian Diabetes, Obesity and Lifestyle Study

Abstract: OBJECTIVE —To determine the population-based prevalence of diabetes and other categories of glucose intolerance (impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]) in Australia and to compare the prevalence with previous Australian data. RESEARCH DESIGN AND METHODS —A national sample involving 11,247 participants aged ≥25 years living in 42 randomly selected areas from the six states and the Northern Territory were examined in a cross-sectional survey using the 75-g oral glucose tolerance test to assess fasting and 2-h plasma glucose concentrations. The World Health Organization diagnostic criteria were used to determine the prevalence of abnormal glucose tolerance. RESULTS —The prevalence of diabetes in Australia was 8.0% in men and 6.8% in women, and an additional 17.4% of men and 15.4% of women had IGT or IFG. Even in the youngest age group (25–34 years), 5.7% of subjects had abnormal glucose tolerance. The overall diabetes prevalence in Australia was 7.4%, and an additional 16.4% had IGT or IFG. Diabetes prevalence has more than doubled since 1981, and this is only partially explained by changes in age profile and obesity. CONCLUSIONS —Australia has a rapidly rising prevalence of diabetes and other categories of abnormal glucose tolerance. The prevalence of abnormal glucose tolerance in Australia is one of the highest yet reported from a developed nation with a predominantly Europid background.

Sleep Apnea as an Independent Risk Factor for All-Cause Mortality : The Busselton Health Study. Commentary

Abstract: Background: Previously published cohort studies in clinical populations have suggested that obstructive sleep apnea (OSA) is a risk factor for mortality associated with cardiovascular disease. However, it is unknown whether sleep apnea is an independent risk factor for all-cause mortality in a community-based sample free from clinical referral bias. Methods: Residents of the Western Australian town of Busselton underwent investigation with a home sleep apnea monitoring device (MESAM IV). OSA was quantified via the respiratory disturbance index (RDI). Mortality status was determined in 397/400 participants (99.3%) after up to 14 years (mean follow-up 13.4 years) by data matching with the Australian National Death Index and the Western Australian Death Register. Univariate analyses and multivariate Cox proportional hazards modelling were used to ascertain the association between sleep apnea and mortality after adjustment for age, gender, body mass index, mean arterial pressure, total cholesterol, high-density lipoprotein cholesterol, diabetes, and medically diagnosed angina in those free from heart attack or stroke at baseline (n = 380). Results: Among the 380 participants, 18 had moderate-severe OSA (RDI ≥15/hr, 6 deaths) and 77 had mild OSA (RDI 5 to <15/hr, 5 deaths). Moderate-to-severe OSA was independently associated with greater risk of all-cause mortality (fully adjusted hazard ratio [HR] = 6.24, 95% CL 2.01,19.39) than non-OSA (n = 285, 22 deaths). Mild OSA (RDI 5 to <15/hr) was not an independent risk factor for higher mortality (HR = 0.47, 95% CL 0.17, 1.29). Conclusions: Moderate-to-severe sleep apnea is independently associated with a large increased risk of all-cause mortality in this community-based sample.

Sleep Apnea as an Independent Risk Factor for All-Cause Mortality: The Busselton Health Study

Abstract: OBSTRUCTIVE SLEEP APNEA (OSA) IS CHARACTERIZED BY REPETITIVE UPPER AIRWAY CLOSURE DURING SLEEP RESULTING IN REPEATED REVERSIBLE blood oxygen desaturation and fragmented sleep. OSA has been associated with a range of pathophysiological changes that impair cardiovascular function,1 including increased blood inflammatory markers and repeated rises in blood pressure during sleep. There is increasing evidence that OSA promotes the development of hypertension, stroke, myocardial infarction and premature death.2 However, because OSA is strongly associated with obesity and thus also with many other obesity-related diseases, it has been difficult to produce clear evidence that these associations are caused by sleep apnea and not other established causes. Better understanding of the association between OSA and mortality risk has major public health importance.3 A number of studies have shown that approximately 25% of middle-aged men and 9% of middle-aged women stop breathing during sleep ≥ 5 times per hour.4–6 Given that the major modifiable risk factor for OSA is obesity it is likely that the prevalence of OSA is increasing.7 Thus, as a very common condition, even modest effects of sleep apnea on morbidity and mortality would be important.3 Previous reports that have independently linked OSA to mortality have all been based on patients referred to sleep clinics.8–14 Two of the most recent and frequently cited of these studies indicated that severe sleep apnea, compared to no sleep apnea, was an independent risk factor for cardiovascular mortality (odds ratio 2.87, 95% CL 1.17, 7.51)12; the other study found that sleep apnea, compared to no sleep apnea, was an independent risk factor for a composite endpoint of all-cause mortality or incident stroke (hazard ratio 1.97, 95% CL 1.12, 3.48).11 However, as these were not community recruited participants they might have been subject to a clinical referral bias that might have given a false impression of the size or significance of the true association with mortality in the community. The choice of composite or restricted mortality endpoints also failed to rule out that sleep apnea might have had some unexpected beneficial effect that reduced mortality from other causes. Data from a community-based cohort, free from clinical referral bias, would thus be useful to determine whether sleep apnea is an independent risk factor for all-cause mortality in middle-aged people. The community of Busselton in Western Australia has been the subject of cross-sectional and follow-up health surveys since 1966.15–17 We aimed to investigate whether sleep apnea is an independent risk factor for all-cause mortality in a sample of Busselton Health Study participants recruited in 1990 to determine the community prevalence of sleep apnea.4

Global Prevalence of Diabetes: Estimates for the year 2000 and projections for 2030

Abstract: OBJECTIVE —The goal of this study was to estimate the prevalence of diabetes and the number of people of all ages with diabetes for years 2000 and 2030. RESEARCH DESIGN AND METHODS —Data on diabetes prevalence by age and sex from a limited number of countries were extrapolated to all 191 World Health Organization member states and applied to United Nations’ population estimates for 2000 and 2030. Urban and rural populations were considered separately for developing countries. RESULTS —The prevalence of diabetes for all age-groups worldwide was estimated to be 2.8% in 2000 and 4.4% in 2030. The total number of people with diabetes is projected to rise from 171 million in 2000 to 366 million in 2030. The prevalence of diabetes is higher in men than women, but there are more women with diabetes than men. The urban population in developing countries is projected to double between 2000 and 2030. The most important demographic change to diabetes prevalence across the world appears to be the increase in the proportion of people >65 years of age. CONCLUSIONS —These findings indicate that the “diabetes epidemic” will continue even if levels of obesity remain constant. Given the increasing prevalence of obesity, it is likely that these figures provide an underestimate of future diabetes prevalence.

Standards of Medical Care in Diabetes

Abstract: 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.

Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study

Abstract: Objective: To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. Design: Prospective observational study. Setting: 23 hospital based clinics in England, Scotland, and Northern Ireland. Participants: 4585 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk. Outcome measures: Primary predefined aggregate clinical outcomes: any end point or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photo-coagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 1% reduction in updated mean HbA 1c adjusted for possible confounders at diagnosis of diabetes. Results: The incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbA 1c was associated with reductions in risk of 21% for any end point related to diabetes (95% confidence interval 17% to 24%, P Conclusions: In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA 1c is likely to reduce the risk of complications, with the lowest risk being in those with HbA 1c values in the normal range (

Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

Abstract: BACKGROUND The effects of empagliflozin, an inhibitor of sodium–glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. METHODS We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin group versus the placebo group. The key secondary composite outcome was the primary outcome plus hospitalization for unstable angina. RESULTS A total of 7020 patients were treated (median observation time, 3.1 years). The primary outcome occurred in 490 of 4687 patients (10.5%) in the pooled empagliflozin group and in 282 of 2333 patients (12.1%) in the placebo group (hazard ratio in the empagliflozin group, 0.86; 95.02% confidence interval, 0.74 to 0.99; P = 0.04 for superiority). There were no significant between-group differences in the rates of myocardial infarction or stroke, but in the empagliflozin group there were significantly lower rates of death from cardiovascular causes (3.7%, vs. 5.9% in the placebo group; 38% relative risk reduction), hospitalization for heart failure (2.7% and 4.1%, respectively; 35% relative risk reduction), and death from any cause (5.7% and 8.3%, respectively; 32% relative risk reduction). There was no significant between-group difference in the key secondary outcome (P = 0.08 for superiority). Among patients receiving empagliflozin, there was an increased rate of genital infection but no increase in other adverse events. CONCLUSIONS Patients with type 2 diabetes at high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care. (Funded by Boehringer Ingelheim and Eli Lilly; EMPA-REG OUTCOME ClinicalTrials.gov number, NCT01131676.)