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Biomedical subjects

D G Bruce

Publications and source records attributed to D G Bruce.

At least 19 recordsLinked to original sources

Characteristics and outcome of type 2 diabetes in urban Aboriginal people: the Fremantle Diabetes Study.

We analysed data from Aboriginal patients with type 2 diabetes recruited to the community-based Fremantle Diabetes Study and compared them with those from the Anglo-Celt participants. Diabetes prevalence among Aboriginal people in the Fremantle area was more than double that of Anglo-Celts and the average age at diagnosis was 14 years or younger. Glycaemic control, urinary albumin :creatinine and the proportion of smokers were all higher in the Aboriginal group and there was evidence of lower diabetes-related quality of life and high rates of disability at a young age. The Aboriginal patients died 18 years or younger than their Anglo-Celt counterparts. Specialized, culturally-sensitive and sustainable programmes are urgently needed to improve the management of diabetes in urban Aboriginal communities.

Activities of Daily Living↗

Vascular depression in older people with diabetes.

AIMS/HYPOTHESIS: Cerebrovascular disease may be causal or a vulnerability factor in late-onset depression and may explain the high rate of depression in older adults with diabetes. We explored a wide range of potential explanatory variables of depression in a longitudinal study of older diabetic subjects to investigate the vascular depression hypothesis in these patients. METHODS: We recruited 207 subjects with diabetes selected for potential cognitive deficits from an existing observational cohort study (average age 75.7 +/- 4.6 years, 52.2% men) for an assessment of depression using a standardised diagnostic instrument (Cambridge Examination for Mental Disorders of the Elderly -- Revised). All subjects underwent a detailed clinical assessment at baseline and at follow-up (after 7.5 +/- 1.1 years). RESULTS: Major depression was present in 45 subjects (21.7%) and minor depression in ten (4.8%). A positive history of strokes and the presence of peripheral arterial disease were significantly associated with depression at the time of diagnosis. In a subsample of 93 cases who underwent structural neuroimaging, the presence of cerebral infarcts was also significantly associated with depression. Treatment with glucose-lowering therapy, higher serum cholesterol levels and difficulties with activities of daily living at baseline were significant predictors of depression at follow-up. CONCLUSIONS/INTERPRETATION: A history of cerebrovascular disease was strongly associated with depression and cerebrovascular risk factors were significant predictors of depression in older diabetic patients. Our findings are consistent with the hypothesis that the excess risk of depression in older diabetic patients is related to underlying cerebrovascular disease.

Aged↗

Predictors, consequences and costs of diabetes-related lower extremity amputation complicating type 2 diabetes: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: The aims of this study were to assess the incidence, predictors, consequences, and inpatient cost of lower extremity amputation (LEA) in a community-based cohort of type 2 diabetic patients. METHODS: Between 1993 and 1996, 1,294 patients with type 2 diabetes were recruited to the longitudinal, observational Fremantle Diabetes Study. LEAs and mortality from cardiac causes were monitored until 30 June 2005. Inpatient costs (in Australian dollars in year 2000), derived using a case-mix approach, were available for the period from 1 July 1993 to 30 June 2000. RESULTS: During follow-up 44 patients without LEA at baseline had a first-ever diabetes-related LEA, an incidence of 3.8 per 1,000 patient-years. Independent predictors of first-ever LEA included foot ulceration (hazard ratio [95% CI]: 5.56 [1.24-25.01]), an ankle brachial index < or =0.90 (2.21 [1.11-4.42]), HbA(1c) (increase of 1%: 1.30 [1.10-1.54]) and neuropathy (2.65 [1.30-5.44]). The risk of cardiac death was significantly increased in patients with LEA at baseline, although this was not an independent risk factor. The median (interquartile range) inpatient cost per LEA admission was 12,485 Australian dollars (6,037 Australian dollars-24,415 Australian dollars), with a median length of stay of 24 (10-43) days. CONCLUSIONS/INTERPRETATION: First-ever LEAs in type 2 patients were associated with poor glycaemic control, foot ulceration and evidence of microvascular and macrovascular disease. Patients with LEA were at increased risk of cardiac death. LEAs contribute disproportionately to diabetes-related inpatient costs.

Aged↗

A prospective study of depression and mortality in patients with type 2 diabetes: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: Depression is associated with excess mortality in patients with type 2 diabetes. We investigated the impact, and possible causal mechanisms, of depression on all-cause and cardiac mortality in patients with type 2 diabetes. METHODS: We recruited 1,273 patients with type 2 diabetes from a postcode-defined community (average age 64.1+/-11.2 years, 48.7% males, median duration of diabetes 4 years [range 1.0-9.0]) and followed them for 7.8+/-2.4 years. Depression was assessed using data obtained using a quality-of-life questionnaire, and cause and date of death were obtained from the state registry. RESULTS: Depression was present in 31.5% of subjects at recruitment. Depressed subjects had a longer duration of diabetes, more cardiovascular risk factors, CHD, cerebrovascular disease and diabetic microvascular complications at baseline, and higher all-cause and cardiac mortality rates during follow-up. In Cox proportional hazards models and after adjustment for demographic and diabetes-related variables and cardiovascular risk factors, depression was significantly associated with excess all-cause and cardiac mortality. When diabetic microvascular and macrovascular complications were added to the Cox models, depression was not significantly associated with excess all-cause or cardiac mortality. CONCLUSIONS/INTERPRETATION: Depression in patients with type 2 diabetes is associated with a greater prevalence of complications but is not an independent predictor of all-cause or cardiac mortality. Depression may contribute to the progression of important prognostic variables in diabetes, particularly macrovascular and microvascular disease.

Aged↗

Predictors of first stroke in Type 1 diabetes: The Fremantle Diabetes Study.

AIMS: To examine prospectively the relationship between vascular risk factors and stroke in Type 1 diabetes. METHODS: A community-based sample of 126 adult Type 1 patients was recruited between 1993 and 1996 and followed annually for a mean+/-sd of 7.2+/-1.6 years. Cerebrovascular events before and after recruitment were identified from history and examination findings, hospital morbidity data and death notifications. RESULTS: Six patients suffered a first stroke during follow-up, of which five were ischaemic and one a subarachnoid haemorrhage on cranial computed tomography. Patients were subdivided into those with no history of stroke/transient ischaemic attack (TIA) at baseline and no subsequent ischaemic stroke (Group 1, n=114), those with a history of stroke/TIA at baseline (Group 2, n=7), and those with no history of stroke/TIA at baseline but who suffered a first ischaemic stroke during follow-up (Group 3, n=5). Group 1 patients were the youngest, had the shortest diabetes duration and were the least likely to be taking antihypertensive medication or aspirin. Amongst a range of potential baseline predictors of first stroke including glycated haemoglobin, only serum HDL-cholesterol differentiated Group 3 patients (0.69+/-0.17 mmol/l) from those in the other groups (1.26+/-0.42 and 1.28+/-0.45 mmol/l for Groups 1 and 2 respectively, P<0.05). CONCLUSIONS: The present association between low serum HDL-cholesterol and ischaemic stroke patients suggests that aggressive management of dyslipidaemia may protect against cerebrovascular disease in Type 1 diabetes.

Aged↗

The incidence of red cell alloantibodies underlying panreactive warm autoantibodies.

A recognized hazard of administering blood transfusions to patients with panreactive warm autoantibodies is that alloantibodies may be masked. Studies have shown the incidence of underlying alloantibodies to be 30 to 40 percent. Adsorption procedures can be used to remove autoantibodies and allow detection and identification of underlying alloantibodies. This study contains data from 126 patients referred to the Red Cell Immunohaematology laboratory at the National Blood Service, Newcastle upon Tyne, United Kingdom. These patients were from the northeast of England, a population for which data have not previously been reported. Samples identified as containing panreactive warm autoantibodies were subjected to adsorption procedures (95 by alloadsorption and 31 by autoadsorption). Absorbed sera were then tested to identify underlying alloantibodies. Of 126 samples, 39 (31%) contained a total of 61 RBC alloantibodies; 15 (12%) contained 2 or more antibody specificities; and 14 (11%) contained alloantibodies not found within the Rh or Kell blood group systems. Antibodies identified included the following specificities: E (19), D (9), c (7), C (6), S (5), Fy(a) (3), Jk(a) (2), Jkb (2), K (2),Kp(a) (2), Fy(b),C(w),N, and f (ce). This study reinforces the value of adsorption studies, whether using autologous or allogeneic RBCs, when panreactive warm autoantibodies are present. In addition, this study confirms that it is not appropriate in these cases simply to issue blood which is "least incompatible" or Rh phenotype- and K antigen-matched.

Autoantibodies↗

Silent myocardial infarction and its prognosis in a community-based cohort of Type 2 diabetic patients: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: Our study investigated the prognosis of Type 2 diabetic patients with silent myocardial infarction in a community-based cohort. METHODS: We analysed data from 1269 patients with Type 2 diabetes mellitus from a community-based observational study of diabetes care, control and complications. Silent myocardial infarction was defined as Q waves (Minnesota codes 1.1, 1.2) on a baseline electrocardiogram in the absence of a history or symptoms of CHD. RESULTS: Silent myocardial infarction was present in 3.9% of patients, or 44% of all Q-wave myocardial infarctions. The patients were subdivided into those with (i). no clinical or Q-wave evidence of myocardial infarction (Group 1), (ii). silent myocardial infarction (Group 2), (iii). self-reported CHD but no Q waves (Group 3), and (iv) self-reported CHD and Q waves (Group 4). Compared to Groups 3 and 4, Group 2 patients were more likely to be women, less likely to have smoked, and had higher serum HDL-cholesterol concentrations and higher blood pressure. Over an average of seven years, and after adjusting for other independent predictors of death, all-cause and CHD mortality were similar in Groups 1 and 2 and greater (twofold for all-cause and fourfold for CHD mortality) in Groups 3 and 4. CONCLUSIONS/INTERPRETATION: Silent myocardial infarction is common in Type 2 diabetes and has a prognosis similar to that in patients without a history of CHD or Q waves.

Aged↗

Autoantibodies to the islet cell antigen SOX-13 are associated with duration but not type of diabetes.

AIMS: The autoantigen SOX-13 of the SRY-related high mobility group box is a low-frequency reactant in sera from patients with Type 1 diabetes. We further investigated the potential diagnostic role of anti-SOX-13, and in particular its ability to distinguish Type 1 from Type 2 diabetes, in two large, well-characterized cohorts. METHODS: SOX-13 autoantibody status was ascertained using a radioimmunoprecipitation assay in (i) a random sample of 546 participants in an Australian community-based study (the Fremantle Diabetes Study; FDS) of whom 119 had Type 1 and 427 Type 2 diabetes, and (ii) a sample of 333 subjects with Type 2 diabetes from the United Kingdom Prospective Diabetes Study (UKPDS) stratified by age, anti-glutamic acid decarboxylase (GAD) and islet cell antibody (ICA) status, and requirement for insulin therapy within 6 years of diagnosis. RESULTS: The frequencies of anti-SOX-13 in the FDS subjects were 16.0% and 14.8% for Type 1 and Type 2 patients, respectively, and levels were similar. In the UKPDS subjects, the frequency was 4.5%. In a logistic regression model involving demographic, anthropometric and metabolic variables, only diabetes duration was significantly associated with anti-SOX-13 positivity, especially for duration > 5 years (P < 0.002). When the coexistence of autoantibodies was assessed in the two study samples, there were no significant associations between anti-SOX-13 and ICA, anti-GAD or ICA512/IA-2. CONCLUSIONS: Whilst the frequency of anti-SOX-13 may be increased in some populations of diabetic patients, this reactivity does not usefully distinguish Type 1 from Type 2 diabetes. However, the association with diabetes duration suggests that anti-SOX-13 may be a non-specific marker of tissue damage associated with chronic hyperglycaemia.

Adult↗

Relationship between testosterone, sex hormone binding globulin and plasma amyloid beta peptide 40 in older men with subjective memory loss or dementia.

In a group of 28 older men with either subjective memory loss or dementia, serum total testosterone and sex hormone binding globulin (SHBG) correlated inversely with plasma levels of amyloid beta peptide 40 (Abeta40, r=-0.5, P=0.01 and r=-0.4, P=0.04, respectively). Calculated free testosterone was also inversely correlated (r=-0.4, P=0.03), and all three relationships remained statistically significant after allowing for age. A similar but non-significant trend was seen with dehydroepiandrosterone sulphate (DHEAS), and neither luteinising hormone (LH) nor estradiol correlated with Abeta40. These data demonstrate that lower androgen levels are associated with increased plasma Abeta40 in older men with memory loss or dementia, suggesting that subclinical androgen deficiency enhances the expression of Alzheimer's disease-related peptides in vivo. An inverse correlation exists between SHBG and Abeta40, warranting further investigation.

Aged↗

Dementia and its associations in type 2 diabetes mellitus: the Fremantle Diabetes Study.

BACKGROUND: recent studies indicate that diabetes is an important risk factor for dementia in older patients, but the cause remains unknown. OBJECTIVES: to determine whether vascular or diabetes-related risk factors predict the development of dementia in older subjects with diabetes. PATIENTS: 63 patients with type 2 diabetes of mean age 75.3 years. METHODS: Subjects were screened for cognitive impairment using the Mini-Mental State Examination (MMSE) and informants who knew the subjects answered the Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE). Probable dementia was diagnosed using highly specific criteria based on the combination of both tests. Potential risk factors for dementia obtained at the time of the cognitive test and annually from a median of 3.2 years previously were examined using univariate methods and simple general linear modelling. RESULTS: since there was a significant association between MMSE and English speaking ability, ten non-Anglo-Celt patients were excluded from the analysis. Probable dementia was diagnosed in six of the remaining 53 subjects (11%). Dementia was significantly and independently associated with higher diastolic and mean arterial blood pressure measurements over the 3 years before assessment. Blood pressure declined over this time in the patients with probable dementia and was similar to that in non-demented subjects at the time of cognitive assessment. CONCLUSIONS: these preliminary data suggest that the high rate of dementia found in older people with diabetes may be explained by the high rate of hypertension in this population.

Aged↗

The relationship between metformin therapy and the fasting plasma lactate in type 2 diabetes: The Fremantle Diabetes Study.

AIMS: To determine (i) which factors, including metformin, are associated with the fasting plasma lactate concentration in type 2 diabetes, and (ii) whether plasma lactate is associated with haemodynamic and metabolic effects. METHODS: We measured fasting plasma lactate in 272 well-characterized diabetic patients from a community-based sample, 181 (67%) of whom were taking metformin with or without other therapies. Linear regression analysis was used to identify predictors, including metformin therapy, of the plasma lactate, and to investigate associations between plasma lactate and resting pulse rate and serum bicarbonate. Factor analysis assessed independent relationships between groups of cosegregating variables. RESULTS: Metformin-treated patients had higher plasma lactate concentrations than nonmetformin-treated subjects (geometric mean [s.d. range] 1.86 [1.34-2.59] vs 1.58 [1.09-2.30] mmol x l(-1), respectively; P < 0.001). In a linear regression model, plasma glucose, BMI and metformin use (but not dose) were independently associated with plasma lactate (P < or = 0.028); after adjustment for the former two variables, metformin-treated patients had a mean plasma lactate 0.16 mmol l-1 greater than in subjects not taking the drug. Factor analysis revealed that plasma lactate, plasma glucose, BMI and pulse rate cosegregated but serum bicarbonate was not in this grouping. CONCLUSIONS: The present results show that metformin therapy increases the fasting plasma lactate in ambulant patients with type 2 diabetes from a community-based cohort. From associations in the data we hypothesize that this increase reflects (i) increased sympathetic activity in patients with the metabolic syndrome (ii) increased substrate (glucose) availability and (iii) a direct metformin effect.

Aged↗

Barriers to community support for the dementia carer: a qualitative study.

OBJECTIVES: To understand how carers of dementia sufferers gain access to community support and to determine potential barriers for carers. DESIGN: Qualitative study using semi-structured interviews of carers after an Aged Care Assessment Team intervention. SETTING: Australian metropolitan Aged Care Assessment Team. SUBJECTS: 24 live-in carers of dementia sufferers. MAIN OUTCOME MEASURES: Carers' subjective experience of sources of stress in their care of the dementia sufferer focusing on interactions with the general practitioner and formal community support agencies. RESULTS: Most carers suffered high levels of stress, mainly due to behaviour disturbances and care needs of the dementia sufferers. Problems with health care agencies were also reported by a majority of the carers to be contributors to their distress. General practitioners were perceived to have referred dementia sufferers late for community care, despite the carer having experienced difficulties for a considerable time period. Carers also complained that too little information was provided about the diagnosis of dementia, how to deal with problem behaviours and how to access support services before and after the assessment procedure. CONCLUSIONS: Problems with the interaction between the carer and the general practitioner appear to be important in delaying access to appropriate support and information. Earlier recognition of carers' problems, the provision of better education and earlier access to support services may lessen the degree of stress experienced by carers.

Adult↗

Autoantibodies to glutamic acid decarboxylase in diabetic patients from a multi-ethnic Australian community: the Fremantle Diabetes Study.

AIMS: To investigate ethnic/racial differences in the prevalence of serum antibodies to glutamic acid decarboxylase (GADA) and ICA512/IA-2 in diabetic patients from a large, urban community. METHODS: A cross-sectional sample of 1,381 diabetic patients aged 11-98 years, representing 61% of those identified in a postcode-defined population base of 120,097 people were studied. Diabetes was classified on clinical grounds. Serum GADA and anti-ICA512/IA-2 were measured by radioimmunoprecipitation assay. RESULTS: Anglo-Celts formed 62% of the sample, southern Europeans 18%, other Europeans 8% and Asians 3%. GADA prevalence in Type 1 and Type 2 diabetes mellitus was 46.0% and 4.2%, respectively, amongst Anglo-Celts and 22.2% and 1.7% in southern Europeans. The prevalence of anti-ICA512/IA-2 in Type 1 diabetes was 17.4% and, in a sample of 233 patients with Type 2 diabetes, 0.8%. GADA-positive Type 2 patients had a lower body mass index and greater glycosylated haemoglobin, and were more likely to be taking insulin, than GADA-negative Type 2 diabetic subjects (P < 0.05), consistent with the phentoype of latent autoimmune diabetes of adults (LADA). In both Type 1 and Type 2 diabetes, there was a strong inverse association between GADA and serum triglycerides (P < 0.001). CONCLUSIONS: The relatively low GADA prevalence in Anglo-Celt patients with Type 1 diabetes is a feature of this community-based study and suggests that GADA levels do fall with time, given the older age of the sample and a relatively long period between diagnosis and sampling. Southern Europeans had an even lower GADA prevalence, regardless of diabetes type. Variations in GADA frequency in diabetic patients of differing European ethnicity has implications for clinical management and healthcare planning.

Adolescent↗

The diagonal ear lobe crease (Frank's sign) is not associated with coronary artery disease or retinopathy in type 2 diabetes: the Fremantle Diabetes Study.

BACKGROUND: The diagonal ear lobe crease (ELC) has been suggested as a simple marker of vascular disease in the general population but there are few data from diabetic patients despite their increased risk of angiopathy. AIM: To determine whether the ELC is a clinically useful sign of coronary artery disease (CAD) or retinopathy in type 2 diabetes. METHODS: One thousand and twenty-two patients from the multi-ethnic urban catchment area of Fremantle Hospital in Western Australia were studied. This sample represents 79% of the type 2 diabetic subjects recruited to the ongoing Fremantle Diabetes Study and 49% of all 2072 patients with type 2 diabetes identified through active case detection in a postcode-defined region of 120,097 people. In addition to other comprehensive data relating to diabetes and its management, the presence of an ELC and evidence of both CAD and retinopathy were ascertained for each patient. RESULTS: The prevalence of ELC was 55%. Patients with an ELC were more likely to have CAD than those without an ELC (p=0.019), but the proportions with retinopathy were not significantly different (p=0.085). The sensitivity and specificity of ELC for detecting CAD were 60% and 48%, and for retinopathy 61% and 47% respectively. The patients with an ELC were significantly older, more likely to be male and had a higher systolic blood pressure than those without (p<0.02). After adjusting for known vascular risk factors, socioeconomic variables and ethnicity in a logistic regression model, an ELC was neither a significant independent predictor of CAD (p=0.45) nor of retinopathy (p=0.14). CONCLUSIONS: The ELC is of little value as a sign of the presence of diabetic vascular complications.

Adult↗

Glycemic control in older subjects with type 2 diabetes mellitus in the Fremantle Diabetes Study.

OBJECTIVES: We investigated whether there were differences in glycemic control in older compared with younger subjects with type 2 diabetes mellitus enrolled in the Fremantle Diabetes Study, a prospective study of diabetes care, control, and complications in an urban setting. DESIGN: Cross-sectional observational study. SETTING: University teaching hospital clinical research center. PARTICIPANTS: A total of 1,205 patients with type 2 diabetes mellitus, 404 (33.3%) of whom were aged over 70 years and 83 (6.9%) aged over 80 years. MEASUREMENTS: Fasting plasma glucose, HbA1c, body mass index, and waist/hip ratio. RESULTS: In multiple linear regression analysis, age was inversely associated with glycemic control whereas duration of diabetes and treatment with either oral hypoglycemic agents or insulin were positively associated with glycemic control. For most age groups there was a significant worsening of glycemic control with duration of diabetes. Octogenarians differed significantly from younger age groups in that those with longer diabetes duration did not demonstrate the increase in hyperglycemia seen in other age groups. As a result, significantly greater proportions of these oldest diabetic subjects had satisfactory glycosylated hemoglobin levels compared with younger subjects. CONCLUSIONS: Octogenarians do not demonstrate the usual progressive deterioration of glycemic control with diabetes duration seen in type 2 diabetes mellitus. The reasons for this difference are unknown but are likely to have clinical significance with regard to therapy and the development of diabetic complications.

Administration, Oral↗

Secondary hyperparathyroidism in patients from Western Australia with hip fracture: relationship to type of hip fracture, renal function, and vitamin D deficiency.

OBJECTIVES: To determine the frequency of vitamin D deficiency and secondary hyperparathyroidism in Australian hip fracture patients living in the community. PATIENTS: A total of 283 consecutive patients with hip fracture admitted over a 15-month period to a university teaching hospital in Western Australia. Included were residents of hostels for the elderly, and excluded were nursing home residents and those with malignant fractures. METHOD: Data collected included biochemistry (25 hydroxyvitamin D, parathyroid hormone and creatinine levels), measurements of function and disability (Barthel Index, Frenchay Activity Index), sunshine exposure, and basic demographics. RESULTS: Vitamin D deficiency occurred in 31.7% and secondary hyperparathyroidism occurred in 17.7% of cases. The major determinants of vitamin D deficiency were outdoor sunshine exposure, ambient daily sunshine, and disability (low Frenchay Activity Index or ADL difficulty). Secondary hyperparathyroidism was related to older age, renal dysfunction, and vitamin D deficiency. Secondary hyperparathyroidism was associated with an excess of trochanteric over subcapital hip fractures. CONCLUSIONS: Secondary hyperparathyroidism appears to be a heterogeneous condition, caused in approximately equal proportions by vitamin D deficiency and renal dysfunction, that may confer increased cortical bone fragility and trochanteric fractures. Renal dysfunction in old age may be an important additional determinant of senile osteoporosis, which has implications for preventive therapy. Vitamin D deficiency occurs in disabled and, presumably, housebound older people despite near optimal climatic conditions.

Activities of Daily Living↗

Secondary hyperparathyroidism, vitamin D deficiency and hip fracture: importance of sampling times after fracture.

There is controversy about how often elevated parathyroid hormone (PTH) levels are found in hip fracture patients. The aim of this study was to determine whether changes in PTH levels after fracture and surgery could explain some of the variation in published data. Blood samples were obtained from 24 elderly patients with hip fracture before surgery, immediately after surgery and at 2 weeks and 3 months after fracture. PTH levels were elevated (> 5.5 pmol) in 33% initially and then fell significantly at 2 weeks in virtually all subjects (P < 0.001) and remained significantly lower after 3 months (n = 17). Although 25-hydroxyvitamin D levels were low (< 30 nmol) in 44% of the patients, the fall in PTH was not explained by alterations in vitamin D metabolites or other measured parameters. The cause of the variation in PTH levels is unknown but measurements immediately after fracture could overestimate the incidence of secondary hyperparathyroidism. Vitamin D deficiency is common in our hip fracture population and is not influenced by hospitalisation.

Aged↗

The effects of sympathetic nervous system activation and psychological stress on glucose metabolism and blood pressure in subjects with type 2 (non-insulin-dependent) diabetes mellitus.

The sympathetic nervous system may contribute to excessive hepatic glucose output in Type 2 (non-insulin dependent) diabetes mellitus and could be implicated in the interrelated problem of hypertension. The aim of these studies was to determine whether subjects with Type 2 diabetes had normal sensitivity (compared with age- and weight-matched non-diabetic subjects) to noradrenaline infusion (60 ng.kg-1.min-1 for 60 min) and to compare the responses with oral tyramine administration (800 mg), and psychological stress (using competitive computer games). Noradrenaline infusion caused significantly greater plasma glucose (mean increment 2.1 +/- 0.4 vs 0.6 +/- 0.1 mmol/l, p less than 0.005) and pressor responses (mean systolic increment 21 +/- 3 vs 11 +/- 1 mmHg, p less than 0.02) in the diabetic subjects. The excessive glycaemia was due to increased hepatic glucose output rather than reduced glucose disposal. Tyramine administration caused significantly increased hepatic glucose output and plasma glucose levels, but with similar responses in the diabetic and non-diabetic subjects; the pulse and pressor responses were also similar between the groups. The psychological stressor induced significant increases in pulse, blood pressure and non-esterified fatty acid levels in the combined group of subjects (p less than 0.01) but did not influence plasma glucose levels in either diabetic or non-diabetic subjects. We conclude that pharmacologically-induced sympathetic nervous stimulation can induce hyperglycaemia. Subjects with uncomplicated Type 2 diabetes have increased sensitivity to exogenous noradrenaline but may not hyperrespond to endogenous sympathetic activation.

Blood Glucose↗