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Biomedical subjects

J R Peters

Publications and source records attributed to J R Peters.

At least 19 recordsLinked to original sources

The health-related utility and health-related quality of life of hospital-treated subjects with type 1 or type 2 diabetes with particular reference to differing severity of peripheral neuropathy.

AIMS/HYPOTHESIS: We characterised symptom severity of diabetic peripheral neuropathy (DPN) in people with diabetes, and correlated this with health-related utility and health-related quality of life. MATERIALS AND METHODS: The study was undertaken in Cardiff and the Vale of Glamorgan, Wales. A postal survey was mailed to a random sample of subjects identified as having diabetes. Data were collected on the symptoms of neuropathy using the Neuropathic Total Symptom Score (self-administered) (NTSS-6-6A) and on quality of life using the Quality of Life in Diabetes Neuropathy Instrument (QoL-DN), EueroQoL five dimensions (EQ5D) and Short Form 36 (SF36). Other information, such as demographics and self-reported drug use, was also collected. The anonymised data were linked to routine inpatient and outpatient healthcare data. RESULTS: Responses were received from 1,298 patients. For patients with a clinically confirmed diagnosis of DPN, the mean NTSS-6-SA score was 6.16 vs 3.19 in patients without DPN (p<0.001). Four categories of severity were defined, ranging from none to severe. All quality of life measures showed a deterioration between these groups: the EQ5D(index) fell from an average of 0.81 in those without symptoms to 0.25 in those with severe symptoms, the SF36 general health profile fell from 59.9 to 25.5 (p<0.001) and the QoL-DN increased from 25.8 to 48.1 (p<0.001). Multivariate models also demonstrated that this relationship remained after controlling for other factors. CONCLUSIONS/INTERPRETATION: This study demonstrated that severity of DPN symptoms was predictive of poor health-related utility and decreased quality of life. Furthermore, it provides detailed utility data for economic evaluation of treatment of typical diabetes-related morbidity states. Reducing DPN morbidity should be a priority.

Adult↗

Low cell pH depresses peak power in rat skeletal muscle fibres at both 30 degrees C and 15 degrees C: implications for muscle fatigue.

Historically, an increase in intracellular H(+) (decrease in cell pH) was thought to contribute to muscle fatigue by direct inhibition of the cross-bridge leading to a reduction in velocity and force. More recently, due to the observation that the effects were less at temperatures closer to those observed in vivo, the importance of H(+) as a fatigue agent has been questioned. The purpose of this work was to re-evaluate the role of H(+) in muscle fatigue by studying the effect of low pH (6.2) on force, velocity and peak power in rat fast- and slow-twitch muscle fibres at 15 degrees C and 30 degrees C. Skinned fast type IIa and slow type I fibres were prepared from the gastrocnemius and soleus, respectively, mounted between a force transducer and position motor, and studied at 15 degrees C and 30 degrees C and pH 7.0 and 6.2, and fibre force (P(0)), unloaded shortening velocity (V(0)), force-velocity, and force-power relationships determined. Consistent with previous observations, low pH depressed the P(0) of both fast and slow fibres, less at 30 degrees C (4-12%) than at 15 degrees C (30%). However, the low pH-induced depressions in slow type I fibre V(0) and peak power were both significantly greater at 30 degrees C (25% versus 9% for V(0) and 34% versus 17% for peak power). For the fast type IIa fibre type, the inhibitory effect of low pH on V(0) was unaltered by temperature, while for peak power the inhibition was reduced at 30 degrees C (37% versus 18%). The curvature of the force-velocity relationship was temperature sensitive, and showed a higher a/P(0) ratio (less curvature) at 30 degrees C. Importantly, at 30 degrees C low pH significantly depressed the ratio of the slow type I fibre, leading to less force and velocity at peak power. These data demonstrate that the direct effect of low pH on peak power in both slow- and fast-twitch fibres at near-in vivo temperatures (30 degrees C) is greater than would be predicted based on changes in P(0), and that the fatigue-inducing effects of low pH on cross-bridge function are still substantial and important at temperatures approaching those observed in vivo.

Animals↗

Characterization and comparison of health-related utility in people with diabetes with various single and multiple vascular complications.

AIMS: To characterize and compare health-related utility in a large cohort of patients treated in hospital with diabetes and with single and multiple comorbidities. METHODS: The study was conducted in Cardiff and the Vale of Glamorgan, UK. Health-related utility was measured using the EQ5D(index), a standardized instrument for measuring health outcome. Patients from the Health Outcomes Data Repository (HODaR) were surveyed by postal questionnaire 6 weeks post discharge for in-patients and during clinics for patients attending as out-patients between January 2002 and July 2005. Patients with diabetes were identified by a previous history of in-patient admission with diabetes or as an out-patient with diabetes recorded as a coexisting diagnosis. RESULTS: We identified 4502 patients with diabetes. Mean ages were 65.4 and 64.2 years for males and females, respectively. Of these, 2003 (45%) had no recorded vascular complication. Overall, the EQ5D(index) was 0.584 (sd 0.325) for males and 0.533 (sd 0.351) for females. For those without any vascular complications the mean EQ5D(index) was 0.735 (sd 0.288). In a general linear model, the presence of single and multiple complications had a detrimental impact on the EQ5D(index). CONCLUSION: The results of this study provide an indication of the true impact of diabetes in terms of health-related utility. There was a decrease in the mean EQ5D(index) for those with vascular complications. Economic models of diabetes that have used additive or multiplicative methods to assess utility in individuals with several complications may be unreliable, and direct measurements, such as this, are recommended.

Aged↗

Evaluation of survival and ischaemic and thromboembolic event rates in patients with non-valvar atrial fibrillation in the general population when treated and untreated with warfarin.

OBJECTIVE: To compare survival and adverse outcome of patients with non-valvar atrial fibrillation (NVAF) treated with or without warfarin. DESIGN: Record linkage method to identify patients with a previous hospital diagnosis of atrial fibrillation and to link these patients to international normalised ratio (INR) test results and mortality data. SETTING: Cardiff and the Vale of Glamorgan, Wales. MAIN OUTCOME MEASURES: Mortality, specifically from ischaemic and thromboembolic events. RESULTS: 6108 patients were identified with NVAF, of whom 36.4% received warfarin. Mean survival in the warfarin and non-warfarin groups was 52.0 months and 38.2 months, respectively (p < 0.001), and 14.4 months (p < 0.001) after adjustment for confounding factors. Warfarin treated patients in the upper quartile of INR control had significantly longer survival (57.5 months) than did those in the lowest quartile of control (38.1 months, p < 0.001). The risk of stroke in the warfarin group when treated was lower than that in the non-warfarin group (relative rate (RR) 0.74, p < 0.001). The risk of death from ischaemic stroke was lower in the warfarin group (RR 0.43, p < 0.001). The risk of all ischaemic and embolic events in the warfarin group was lower when they were taking warfarin (RR 0.74, p < 0.001). The risk of bleeding in the warfarin group when treated was greater (RR 1.78, p = 0.001). CONCLUSIONS: Patients with NVAF within the recommended target INR range of 2.0-3.0 survive longer and have reduced morbidity. Probably too few people are anticoagulated with warfarin in NVAF.

Aged↗

Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population.

OBJECTIVE: To evaluate how well patients with non-valvar atrial fibrillation (NVAF) were maintained within the recommended international normalised ratio (INR) target of 2.0-3.0 and to explore the relation between achieved INR control and clinical outcomes. DESIGN: Record linkage study of routine activity records and INR measurements. SETTING: Cardiff and the Vale of Glamorgan, South Wales, UK. PARTICIPANTS: 2223 patients with NVAF, no history of heart valve replacement, and with at least five INR measurements. MAIN OUTCOME MEASURES: Mortality, ischaemic stroke, all thromboembolic events, bleeding events, hospitalisation, and patterns of INR monitoring. RESULTS: Patients treated with warfarin were outside the INR target range 32.1% of the time, with 15.4% INR values > 3.0 and 16.7% INR values < 2.0. However, the quartile with worst control spent 71.6% of their time out of target range compared with only 16.3% out of range in the best controlled quartile. The median period between INR tests was 16 days. Time spent outside the target range decreased as the duration of INR monitoring increased, from 52% in the first three months of monitoring to 30% after two years. A multivariate logistic regression model showed that a 10% increase in time out of range was associated with an increased risk of mortality (odds ratio (OR) 1.29, p < 0.001) and of an ischaemic stroke (OR 1.10, p = 0.006) and other thromboembolic events (OR 1.12, p < 0.001). The rate of hospitalisation was higher when INR was outside the target range. CONCLUSIONS: Suboptimal anticoagulation was associated with poor clinical outcomes, even in a well controlled population. However, good control was difficult to achieve and maintain. New measures are needed to improve maintenance anticoagulation in patients with NVAF.

Aged↗

Evaluating the performance of the Framingham risk equations in a population with diabetes.

AIMS: The Framingham risk equations are widely used to estimate risk of coronary heart disease (CHD). The purpose of this study was to evaluate the reliability of these equations in predicting CHD risk in people with diabetes and the reliability of using imputed mean HDL-cholesterol values. METHODS: Data describing the baseline characteristics of recognized CHD risk factors for 938 people aged 30-74 years were extracted from the Cardiff Diabetes Database. Data describing CHD events were available for up to 4 years following the baseline year (1996). Several mathematical techniques were used to assess the reliability of predictions provided by the Framingham equations in this population. RESULTS: Thirty-four percent of males and 25% of females who experienced CHD events had a predicted 10-year CHD risk >/= 30%. Seventy-five percent of males and 58% of females had a predicted 10-year CHD risk >/= 20%. Using imputed HDL-cholesterol values, 26% of males and 6% of females who later developed CHD events had a 10-year CHD risk >/= 30%. Using imputed HDL-cholesterol values, the CHD risk predicted by the Framingham equations consistently underestimated the actual risk of CHD events. However, refitting the Framingham risk equations to the Cardiff data resulted in only marginal improvements in discriminatory capabilities. CONCLUSIONS: The Framingham risk equations can be unreliable when applied to the diabetic population, tending to underestimate an individual's probability of progressing to CHD; the equations perform marginally better in women than in men. The use of imputed mean HDL-cholesterol values improved the reliability of the estimates of risk.

Adult↗

Abnormal metabolic fate of nitric oxide in Type I diabetes mellitus.

AIMS/HYPOTHESIS: Reduced bioavailability of endothelium-derived nitric oxide is implicated in diabetic macrovascular and microvascular disease. In patients with diabetes, we hypothesised that protein glycosylation can alter nitric oxide binding affinity of haemoglobin and plasma proteins, hence reducing nitric oxide availability and causing an alteration in nitric oxide metabolism. METHODS: Binding of nitric oxide to haemoglobin was studied across a range of glycosylation levels in vitro (HbA(1c) 5.9 to 9.8%). In clinical studies nitrate, nitrite, nitrosyl haemoglobin and plasma nitrosothiols were measured in venous blood from 23 patients with uncomplicated Type I (insulin-dependent) diabetes mellitus and 17 non-diabetic control subjects. Samples were analysed at baseline and after nitric oxide was added ex vivo. RESULTS: Nitric oxide-haemoglobin binding was increased at a HbA(1c) greater than 8.5% compared with 5.9% (p<0.01). Basal nitrosyl haemoglobin was higher in diabetic patients compared with the control subjects (0.59+/-0.12 micro mol/l vs 0.24+/-0.12 micro mol/l, p<0.05). Plasma nitrosothiols, and nitrite and nitrate (NOx) concentrations were similar in diabetic patients compared with the control subjects (7.64+/-0.79 micro mol/l vs 5.93+/-0.75 micro mol/l, 13.98+/-2.44 micro mol/l vs 12.44+/-2.15 micro mol/l, respectively). In blood from diabetic patients, added nitric oxide was metabolised preferentially to nitrosyl haemoglobin and plasma nitrosothiols, with a twofold increase in nitrosyl haemoglobin observed across all concentrations of nitric oxide (p<0.05). These preferential increases correlated positively with HbA(1c). CONCLUSION/INTERPRETATION: Nitrosyl haemoglobin is increased in patients with Type I diabetes. Preferential metabolism to nitrosyl haemoglobin and nitrosothiols occurs after increases in nitric oxide. Our results show an accentuated association between nitric oxide and glycosylated proteins, especially deoxygenated haem. An altered metabolic fate of nitric oxide could influence microvascular regulation and tissue perfusion.

Adult↗

Screening for gestational diabetes; past, present and future.

Gestational diabetes is carbohydrate intolerance, with onset or first recognition of hyperglycaemia during pregnancy. Several studies have suggested that gestational hyperglycaemia is associated with adverse maternal and fetal outcomes, promoting the case for screening. Conversely, others argue that screening for gestational diabetes may colour the clinical judgement, influencing further management, e.g. more 'unjustified' caesarean sections. Additionally, the lack of definitive data either on a clear-cut glycaemic threshold for the development of adverse outcomes or on the impact of intervention is emphasized by opponents of screening. This review attempts to evaluate the available data on screening for gestational diabetes. Oral glucose tolerance test is promoted on the basis that the diabetogenic stress of pregnancy is encountered during late gestation and is best recognized in the fed state. There are different tests, including the 1 h/50-g, 2 h/75-g and 3 h/100-g tests, with practical limitations, including the time and cost involved and the unpleasant supra-physiological glucose load that is unrelated to body weight, and issues of reproducibility and sensitivity/specificity profiles. Despite its convenience, the poor sensitivity of random glucose has precluded its routine use for screening. Fasting glucose appears to be promising but further testing is required to ensure satisfactory sensitivity/specificity in different populations. Despite its limitations, the oral glucose tolerance test has become established as the 'most acceptable' diagnostic test for gestational diabetes. More convenient methods, e.g. fasting or random or post-load glucose, have to be validated therefore against the oral glucose tolerance test to gain acceptance for routine screening.

Blood Glucose↗

Evaluation of a hospital diabetes specialist nursing service: a randomized controlled trial.

AIMS: To evaluate the effectiveness and cost implications of a hospital diabetes specialist nursing service. METHODS: We conducted a prospective, open, randomized, controlled trial of standard in-patient care for adults with diabetes, with and without the intervention of a diabetes specialist nursing (DSN) service. The setting was a single UK university hospital. SUBJECTS: were unselected patients referred to the hospital DSN service. Primary outcome measures were length of hospital stay and patterns of readmission (frequency and time to first readmission). Secondary outcome measures were subjects' diabetes-related quality of life, diabetes knowledge score, satisfaction with treatment, and GP and community care contacts following discharge. Costs were estimated from the hospital and published sources. RESULTS: Median length of stay was lower in the intervention group (11.0 vs. 8.0 days, P < 0.01). Readmission rates were the same in the two groups (25%), and mean time to readmission was similar in the two groups, although slightly less in the control group (278 vs. 283 days, P = 0.80). The cost per patient for nursing input was 38.94 pounds sterling. However, when the reduced length of stay was accounted for, the intervention produced a mean cost per admission of 436 ponds sterling lower than that of the control group (P = 0.19). Patients in the intervention group were more knowledgeable regarding their diabetes and more satisfied with their care. CONCLUSIONS: Diabetes specialist nurses are potentially cost saving by reducing hospital length of stay (LOS). There was no evidence of an adverse effect of reduced LOS on re-admissions, use of community resources, or patient perception of quality of care.

Adult↗

Relative activity and referral patterns for diabetes and non-diabetes in general practice.

AIMS: To describe and compare general practice (GP) activity for patients with and without diabetes using a survey of general practices representing over 10% of the Welsh population. METHODS: The Welsh GP Morbidity Database Project (GPMDP) collected data including demographic and lifestyle information and consultation data such as diagnosis, referral and surgical procedures. These data were analysed to establish the annual period prevalence of diabetes and compare the relative number of consultations and referrals. RESULTS: A total of 4,182 diabetic patients were recorded (prevalence 1.41%) and accounted for 77,371 (4.4%) consultations. Patients with diabetes were four-times more likely to be referred to community services (relative risk (RR) 4.1, 95% CI 3.7-4.7), in particular district nursing (RR 3.8, 1.9-7.7), optician services (RR 8.9, 5.0-15.7), chiropody (RR 8.2 6.4-10.5) and dietician services (RR 21.2, 17.6-25.5). Patients with diabetes were also more likely to be followed-up in general practice (RR 6.7, 6.2-7.2) both within 1 month (RR 6.7, 6.2-7.2) and 1 month to 1 year (RR 9.7, 8.9-10.7). Emergency admissions were also more likely for patients with diabetes (RR 6.8, 6.2-7.5) as were elective admissions to general medicine (RR 5.6, 4.6-6.7), surgery (RR 1.8, 1.5-2.0) and opthalmology (4.2, 3.4-5.2). CONCLUSION: The increased utilization of health services apparent in secondary care was confirmed in primary care. Further research is required to determine levels of community activity after initial referral.

Adolescent↗

Estimating the prevalence of diagnosed diabetes in a health district of Wales: the importance of using primary and secondary care sources of ascertainment with adjustment for death and migration.

AIMS: To determine diagnosed diabetic prevalence within our district (population 434398) in 1996 using data from two sources. METHODS: A general practice audit comprising data on patients with diabetes from 61 (82%) of 74 general practices was linked to a record linkage-derived patient index in which data from secondary care and other sources underwent a process of probability matching to identify records relating to the same patient and to flag those with diabetes. By linking this dataset to a mortality dataset, patients known to have died before 1996 could be excluded. Age and sex-stratified emigration rates were applied to those identified by the hospital dataset for each year from 1991 onwards. RESULTS: A total of 386988 residents (89.1%) were listed with a general practitioner participating in the audit, of whom 6050 patients were identified as having diabetes in 1996; a prevalence rate of 1.56%. From the hospital-based source, 7639 patients were identified who were alive in 1996, a period prevalence of 1.76%. By combining the two sources, and extrapolating the general practice audit to the population as a whole, a total of 10 530 patients were identified of whom 8735 were confirmed as still resident within South Glamorgan during 1996. This represented a period prevalence of between 2.01% to 2.42%. By applying age and sex-stratified migration rates to the diabetic population identified by hospital sources, a diagnosed diabetic population of 10,004 was identified, a prevalence of 2.3%. CONCLUSIONS: This study demonstrates that to calculate the true prevalence of diagnosed diabetes from health sources, it is necessary to use both primary and secondary care sources.

Adolescent↗

The prevalence of multiple diabetes-related complications.

AIMS: To determine the prevalence of the complications of diabetes and the interrelationship between them within a United Kingdom district health authority population. METHODS: Data extracted from a general practice diabetes audit were combined with data for patients with diabetes derived from a patient index constructed using record linkage techniques. RESULTS: A total of 10709 patients were identified as having diabetes (prevalence 2.47%). Coronary heart disease was present in 25.2%, cerebrovascular disease in 9.6%, complications of the 'diabetic foot' in 18.1%, retinopathy in 16.5% and nephropathy in 2.0%. Over a half of the patients (52.1%) had none of the studied complications, 30.2% had one, 12.7% had two, 4.1% had three, 0.8% had four and 0.1% had all five. All complications were related to both age and duration of diabetes but duration was particularly apparent for the microvascular complications (retinopathy and nephropathy). Macrovascular complications in the Type 2 diabetic population appear advanced in onset compared with Type 1. CONCLUSIONS: Multiple complications are apparent in almost one fifth of patients with diabetes. Macrovascular morbidity in Type 2 diabetes of early onset indicates that a targeted approach to treatment may prove most beneficial in both patient and health service terms.

Adolescent↗

The cost of diabetes: time for a different approach?

We argue that studies estimating the treatment cost of diabetes and other economic issues have progressed dramatically over recent years. This has undoubtedly improved our understanding of diabetes. However, attention needs to now shift to more detailed studies that require prospective bespoke data collection from epidemiologists as well as economists. This is not to say that investigation of costs using routine data is of no value--such work will continue to provide new data and methods to those evaluating new interventions, as well as by helping to identify important research areas. However, it may be time for a new paradigm to help in our understanding of this challenging disease. Such an approach must be capable of supporting the complex evaluation of new technologies, and subsequently, can not rely solely on routine data.

Diabetes Mellitus↗

Relationship between diabetes and mortality: a population study using record linkage.

OBJECTIVE: To determine patterns and causes of mortality for patients with diabetes in a district health authority RESEARCH DESIGN AND METHODS: The study used cross-sectional record linkage, combining an electronic death register with a diabetic patient register constructed from a variety of routine health data sources collected from 1991 to 1997. The study was conducted in Cardiff and the Vale of Glamorgan, Wales, U.K., and included all diabetic deaths between 1993 and 1996. RESULTS: Of 1,694 deaths in patients with known diabetes, only 674 (39.8%) had diabetes recorded as an immediate or antecedent cause of death. Mortality rates were 41.8 per 1,000 for the diabetic population and 10.1 per 1,000 for the nondiabetic population. The standard mean ratio for the diabetic population was 1.24 (95% CI 1.12-1.35), with the risk of mortality relative to the nondiabetic population decreasing with age. Males with diabetes lost an average of 7.0 years from the year of diagnosis, and females with diabetes lost an average of 7.5 years. The most common cause of death was cardiovascular disease, which accounted for 49.1% of deaths in the diabetic population. CONCLUSIONS: Diabetes is recorded as a cause of death on a minority of death certificates for patients with diabetes. Using death certificates in isolation, therefore, is a poor method of estimating diabetic mortality, but results can be improved with the use of record linkage techniques. Patients with diabetes have an excess risk of mortality compared with the nondiabetic population. Life-years lost for patients with diabetes is strongly related to age at diagnosis and is a means of expressing mortality without relying on accurate prevalence data.

Adult↗

Electron spin resonance spectroscopy, exercise, and oxidative stress: an ascorbic acid intervention study.

Oxygen free radicals are highly reactive species that are produced in increased quantities during strenuous exercise and can damage critical biological targets such as membrane phospholipids. The present study examined the effect of acute ascorbic acid supplementation on exercise-induced free radical production in healthy subjects. Results demonstrate increases in the intensity of the alpha-phenyl-tert-butylnitrone adduct (0.05 +/- 0.02 preexercise vs. 0.19 +/- 0.03 postexercise, P = 0.002, arbitrary units) together with increased lipid hydroperoxides (1.14 +/- 0.06 micromol/l preexercise vs. 1.62 +/- 0.19 micromol/l postexercise, P = 0.005) and malondialdehyde (0.70 +/- 0.04 micromol/l preexercise vs. 0.80 +/- 0.04 micromol/l postexercise, P = 0.0152) in the control phase. After supplementation with ascorbic acid, there was no significant increase in the electron spin resonance signal intensity (0.02 +/- 0. 01 preexercise vs. 0.04 +/- 0.02 postexercise, arbitrary units), lipid hydroperoxides (1.12 +/- 0.21 micromol/l preexercise vs. 1.12 +/- 0.08 micromol/l postexercise), or malondialdehyde (0.63 +/- 0.07 micromol/l preexercise vs. 0.68 +/- 0.05 micromol/l postexercise). The results indicate that acute ascorbic acid supplementation prevented exercise-induced oxidative stress in these subjects.

Adolescent↗

Atrial natriuretic peptide in type 2 diabetes mellitus: response to a physiological mixed meal and relationship to renal function.

Relatively few data exist on atrial natriuretic peptide (ANP) characteristics in Type 2 diabetes mellitus (DM). Therefore, plasma immunoreactive ANP concentrations were measured before and for 4 h following the ingestion of a physiological mixed meal in 8 newly diagnosed, normotensive, normoalbuminuric, patients with Type 2 DM and 6 normotensive, non-diabetic controls. In patients with Type 2 DM, basal plasma ANP concentrations were 4.0 +/- 2.0 and not significantly changed following ingestion of the meal, with peak levels of 4.9 +/- 2.8 pmol l(-1). Non-diabetic controls had higher basal plasma ANP concentrations, 8.7 +/- 3.4 pmol l(-1) (p < 0.05), significantly increasing to a peak of 11.9 +/- 6.3 pmol l(-1) at 30 min post meal. Extracellular fluid volume (ECV) was not different between diabetic patients and controls (15877 +/- 2679 vs 13668 +/- 1792 ml3). Glomerular filtration rate (GFR) (isotopic clearance corrected for body surface area) was elevated in diabetic patients (mean +/- SD) 130 +/- 39 vs 98 +/- 10 ml min(-1), p < 0.05). For the DM subjects, basal ANP levels were negatively correlated with GFR (rs - 0.74, p < 0.05) and effective renal plasma flow (ERPF) (rs - 0.8, p < 0.05). We conclude that patients with Type 2 DM demonstrate reduced basal plasma ANP concentrations which are inversely correlated to renal function. In contrast to non-diabetic controls, ANP in Type 2 DM does not rise in response to feeding.

Adult↗