The association between meat intake and the risk of coronary heart disease in Korean men using the Framingham risk score: A prospective cohort study.

BACKGROUND AND AIMS: Research suggests that meat intake may increase the risk of coronary heart disease (CHD), but most studies take place in Western countries, where the types and amount of meat products consumed differ from those in Asian countries. We aimed to identify the association between meat intake and CHD risk in Korean male adults, using the Framingham risk score. METHODS AND RESULTS: We used data from the Korean Genome and Epidemiology Study (KoGES) Health Examinees (HEXA) study, including 13,293 Korean male adults. We estimated the association of meat intake with ≥20% 10-year CHD risk using Cox proportional hazards regression models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Subjects with the highest total meat intake had a 53% (model 4: HR 1.53, 95% CI 1.05-2.21) increased 10-year CHD risk compared to those with the lowest intake. Those with the highest red meat intake had a 55% (model 3: HR 1.55, 95% CI 1.16-2.06) increased 10-year CHD risk compared to those with the lowest intake. No association was observed between poultry or processed meat intake and 10-year CHD risk. CONCLUSIONS: Consumption of total meat and red meat was associated with a higher risk of CHD in Korean male adults. Further studies are needed to provide criteria for the appropriate meat intake by meat type to reduce CHD risk.

Association of milk consumption with management and incidence of hypertension among South Korean adults: A prospective analysis of the health examinees study cohort.

BACKGROUND AND AIMS: Studies have revealed a positive relationship between milk consumption and hypertension. However, few researchers have investigated the association between milk consumption and changes in blood pressure (BP) in South Korean adults. Therefore, we examined the association between milk intake and the management and risk of hypertension in South Korean adults. METHODS AND RESULTS: Participants were selected from the Health Examinees study. The definition of hypertension was based on the guidelines of the Korean Society of Hypertension. The participants were divided into three groups according to changes between baseline and follow-up BP data. Milk consumption was assessed using food frequency questionnaires. In both men and women, the higher milk consumption group had increased odds of trends of BP improvement (OR: 1.249, 95% CI: 1.043-1.496, p for trend: 0.2271 in men; OR: 1.147, 95% CI: 1.014-1.297, p for trend: 0.0293 in women) and decreased odds of trends of worsening (OR: 0.861, 95% CI: 0.756-0.980, p for trend: <0.0001 in men, OR: 0.866, 95% CI: 0.794-0.943, p for trend: 0.0010 in women) compared to those of the non-consumption group. In the prospective study, milk intake was inversely associated with hypertension risk (HR: 0.900, 95% CI: 0.811-0.999, p for trend: 0.0076 in men; HR: 0.879, 95% CI: 0.814-0.949, p for trend: 0.0002 in women). CONCLUSION: Increased intake of milk was inversely related to the risk of increased BP, with a decreased risk of hypertension events.

Empagliflozin modulates renal sympathetic and heart rate baroreflexes in a rabbit model of diabetes.

AIMS/HYPOTHESIS: We determined whether empagliflozin altered renal sympathetic nerve activity (RSNA) and baroreflexes in a diabetes model in conscious rabbits. METHODS: Diabetes was induced by alloxan, and RSNA, mean arterial pressure (MAP) and heart rate were measured before and after 1 week of treatment with empagliflozin, insulin, the diuretic acetazolamide or the ACE inhibitor perindopril, or no treatment, in conscious rabbits. RESULTS: Four weeks after alloxan administration, blood glucose was threefold and MAP 9% higher than non-diabetic controls (p < 0.05). One week of treatment with empagliflozin produced a stable fall in blood glucose (-43%) and increased water intake (+49%) but did not change RSNA, MAP or heart rate compared with untreated diabetic rabbits. The maximum RSNA to hypotension was augmented by 75% (p < 0.01) in diabetic rabbits but the heart rate baroreflex was unaltered. Empagliflozin and acetazolamide reduced the augmentation of the RSNA baroreflex (p < 0.05) to be similar to the non-diabetic group. Noradrenaline (norepinephrine) spillover was similar in untreated diabetic and non-diabetic rabbits but twofold greater in empagliflozin- and acetazolamide-treated rabbits (p < 0.05). CONCLUSIONS/INTERPRETATION: As empagliflozin can restore diabetes-induced augmented sympathetic reflexes, this may be beneficial in diabetic patients. A similar action of the diuretic acetazolamide suggests that the mechanism may involve increased sodium and water excretion. Graphical abstract.

Differential sympathetic response to lesion-induced chronic kidney disease in rabbits.

Chronic kidney disease (CKD) is associated with greater sympathetic nerve activity but it is unclear if this is a kidney-specific response or due to generalized stimulation of sympathetic nervous system activity. To determine this, we used a rabbit model of CKD in which quantitative comparisons with control rabbits could be made of kidney sympathetic nerve activity and whole-body norepinephrine spillover. Rabbits either had surgery to lesion 5/6th of the cortex of one kidney by electro-lesioning and two weeks later removal of the contralateral kidney, or sham lesioning and sham nephrectomy. After three weeks, the blood pressure was statistically significantly 20% higher in conscious rabbits with CKD compared to rabbits with a sham operation, but their heart rate was similar. Strikingly, kidney nerve activity was 37% greater than in controls, with greater burst height and frequency. Total norepinephrine spillover was statistically significantly lower by 34%, and kidney baroreflex curves were shifted to the right in rabbits with CKD. Plasma creatinine and urine output were elevated by 38% and 131%, respectively, and the glomerular filtration rate was 37% lower than in sham-operated animals (all statistically significant). Kidney gene expression of fibronectin, transforming growth factor-ß, monocyte chemotactic protein1, Nox4 and Nox5 was two- to eight-fold greater in rabbits with CKD than in control rabbits. Overall, the glomerular layer lesioning model in conscious rabbits produced a moderate, stable degree of CKD characterized by elevated blood pressure and increased kidney sympathetic nerve activity. Thus, our findings, together with that of a reduction in total norepinephrine spillover, suggest that kidney denervation, rather than generalized sympatholytic treatments, may represent a preferable management for CKD associated hypertension.

Factors Responsible for Obesity-Related Hypertension.

PURPOSE OF REVIEW: The major health issue of being overweight or obese relates to the development of hypertension, insulin resistance and diabetic complications. One of the major underlying factors influencing the elevated blood pressure in obesity is increased activity of the sympathetic nerves to particular organs such as the kidney. RECENT FINDINGS: There is now convincing evidence from animal studies that major signals such as leptin and insulin have a sympathoexcitatory action in the hypothalamus to cause hypertension. Recent studies suggest that this may involve 'neural plasticity' within hypothalamic signalling driven by central actions of leptin mediated via activation of melanocortin receptor signalling and activation of brain neurotrophic factors. This review describes the evidence to support the contribution of the SNS to obesity related hypertension and the major metabolic and adipokine signals.

Comparison of sympathetic nerve activity normalization procedures in conscious rabbits.

One of the main constraints associated with recording sympathetic nerve activity (SNA) in both humans and experimental animals is that microvolt values reflect characteristics of the recording conditions and limit comparisons between different experimental groups. The nasopharyngeal response has been validated for normalizing renal SNA (RSNA) in conscious rabbits, and in humans muscle SNA is normalized to the maximum burst in the resting period. We compared these two methods of normalization to determine whether either could detect elevated RSNA in hypertensive rabbits compared with normotensive controls. We also tested whether either method eliminated differences based only on different recording conditions by separating RSNA of control (sham) rabbits into two groups with low or high microvolts. Hypertension was induced by 5 wk of renal clipping (2K1C), 3 wk of high-fat diet (HFD), or 3 mo infusion of a low dose of angiotensin (ANG II). Normalization to the nasopharyngeal response revealed RSNA that was 88, 51, and 34% greater in 2K1C, HFD, and ANG II rabbits, respectively, than shams (P < 0.05), but normalization to the maximum burst showed no differences. The RSNA baroreflex followed a similar pattern whether RSNA was expressed in microvolts or normalized. Both methods abolished the difference between low and high microvolt RSNA. These results suggest that maximum burst amplitude is a useful technique for minimizing differences between recording conditions but is unable to detect real differences between groups. We conclude that the nasopharyngeal reflex is the superior method for normalizing sympathetic recordings in conscious rabbits.

Accelerated age-related decline in renal and vascular function in female rats following early-life growth restriction.

Many studies report sexual dimorphism in the fetal programming of adult disease. We hypothesized that there would be differences in the age-related decline in renal function between male and female intrauterine growth-restricted rats. Early-life growth restriction was induced in rat offspring by administering a low-protein diet (LPD; 8.7% casein) to dams during pregnancy and lactation. Control dams were fed a normal-protein diet (NPD; 20% casein). Mean arterial pressure (MAP) and renal structure and function were assessed in 32- and 100-wk-old offspring. Mesenteric artery function was examined at 100 wk using myography. At 3 days of age, body weight was ∼24% lower (P < 0.0001) in LPD offspring; this difference was still apparent at 32 wk but not at 100 wk of age. MAP was not different between the male NPD and LPD groups at either age. However, MAP was greater in LPD females compared with NPD females at 100 wk of age (∼10 mmHg; P < 0.001). Glomerular filtration rate declined with age in the NPD male, LPD male and LPD female offspring (∼45%, all P < 0.05), but not in NPD female offspring. Mesenteric arteries in the aged LPD females had reduced sensitivity to nitric oxide donors compared with their NPD counterparts, suggesting that vascular dysfunction may contribute to the increased risk of disease in aged females. In conclusion, females growth-restricted in early life were no longer protected from an age-related decline in renal and arterial function, and this was associated with increased arterial pressure without evidence of renal structural damage.

Differential activation of renal sympathetic burst amplitude and frequency during hypoxia, stress and baroreflexes with chronic angiotensin treatment.

NEW FINDINGS: What is the central question of this study? Is the elevated tonic renal nerve activity induced by chronic angiotensin administration mediated by recruitment or increased firing frequency and does this occur via stress, chemoreflex or baroreflex pathways? What is the main finding and its importance? Long-term angiotensin treatment in rabbits elevates renal sympathetic nerve activity by recruitment of previously silent fibres. This was similar to the effect of chemoreflex stimulation, but not to stress or baroreceptor activation, suggesting that presympathetic pathways activated by angiotensin may be common to those activated by chemoreceptors. Modulation of sympathetic nerve activity involves control by the CNS of the amplitude of neural discharges, reflecting recruitment of neurons and their firing frequency. We tested whether elevated tonic renal sympathetic nerve activity (RSNA) induced by chronic angiotensin administration is mediated by recruitment or increased firing frequency and whether this is characteristic of the pattern observed with activation of stress, chemoreflex or baroreflex pathways. Conscious rabbits treated with angiotensin II for 12 weeks to increase blood pressure by 10-30% were subjected to stress (air jet), hypoxia (10% O2 + 3% CO2) and drug-induced changes in blood pressure to produce baroreflexes. Total RSNA and RSNA burst amplitude were scaled to 100 normalized units (n.u.) by the maximal response to smoke. After 12 weeks of treatment, blood pressure was 17% higher than baseline 68 ± 1 mmHg (P = 0.02). Compared with sham treatment, total RSNA and burst amplitude were +82% (P < 0.001) and 39% (P = 0.04) greater, but burst frequency was similar. Total RSNA increased during hypoxia (+38% from 4.9 ± 0.7 n.u.), owing to greater amplitude, but not frequency. Air-jet stress increased total RSNA (+44% from 4.3 ± 0.5 n.u.) and burst frequency (+21% from 5.4 ± 0.7 bursts s(-1) ), but not amplitude. Angiotensin enhanced total RSNA responses to both air jet (+33%) and hypoxia (+58%), but only increased the amplitude response to air jet. The RSNA baroreflexes reset to the higher blood pressure, but amplitude or frequency was not differentially altered. Chronic angiotensin treatment elevated RSNA by recruitment of neurons, which is similar to chemoreflex stimulation, but not to stress or baroreceptor activation, suggesting that presympathetic pathways activated by angiotensin may be common to those activated by chemoreceptors.

Central nervous system dysfunction in obesity-induced hypertension.

The activation of the sympathetic nervous system is a major mechanism underlying both human and experimental models of obesity-related hypertension. While insulin and the adipokine leptin have long been thought to contribute to obesity-related neurogenic mechanisms, the evidence is now very strong that they play a major role, shown particularly in animal studies using selective receptor antagonists. There is not just maintenance of leptin's sympatho-excitatory actions as previously suggested but considerable amplification particularly in renal sympathetic nervous activity. Importantly, these changes are not dependent on short-term elevation or reduction in plasma leptin or insulin, but require some weeks to develop indicating a slow "neural adaptivity" within hypothalamic signalling. These effects can be carried across generations even when offspring are raised on a normal diet. A better understanding of the underlying mechanism should be a high research priority given the prevalence of obesity not just in the current population but also for future generations.

Association of hypertension with noodle consumption among Korean adults based on the Health Examinees (HEXA) study.

BACKGROUND/OBJECTIVES: The prevalence of hypertension is increasing, and noodles have a high sodium content, so noodle consumption might be associated with a higher prevalence of hypertension. This study aimed to analyze the association between total and types of noodle intake and the risk of hypertension among Korean adults. Subjects aged 40-69 years were selected for this study. SUBJECTS/METHODS: This study included 56,580 participants (18,246 men and 38,334 women) aged 40-69 years old from the Health Examinees study. Noodle and nutrient intakes were assessed using the food frequency questionnaire. Hypertension was diagnosed as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or antihypertensive medication use. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for hypertension. RESULTS: Higher noodle consumption was associated with increased hypertension among men (HR, 1.273; 95% CI, 1.166-1.390) and women (HR, 1.116; 95% CI, 1.038-1.199). CONCLUSION: We recommended reducing noodle intake and consuming vegetables and fruits to increase potassium intake, which can prevent vascular diseases.

Edible mushroom intake and risk of all-cause and cause-specific mortality: results from the Korean Genome and Epidemiology Study (KoGES) Cohort.

Mushroom is rich in protein, fiber, vitamins, and essential amino acids. A relationship between mushroom consumption and a lower all-cause mortality risk has been reported. This study aimed to examine the association of mushroom consumption with all-cause and cause-specific mortality. Data were extracted from the Korean Genome and Epidemiology Study cohort. Mortality outcomes were confirmed from 2001-2020 death records provided by the Korea National Statistical Office. Mushroom intake was assessed using food frequency questionnaires and categorized into four groups: none, <1 serving per week, 1-3 servings per week, and ≥3 servings per week. Cox proportional hazard regression was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. The 152 828 participants ≥40 years had a mean age of 53.7 years. Over a mean 11.6-year follow-up, 7085 deaths were recorded. In men, consuming <1 and 1-3 servings per week of mushroom was associated with lower risks of all-cause (HR = 0.858, 95% CI = 0.793-0.929; HR = 0.902, 95% CI = 0.819-0.993) and cardiovascular disease (CVD) (HR = 0.767, 95% CI = 0.632-0.930; HR = 0.762, 95% CI = 0.601-0.967) mortality than non-consumption. In women, consuming <1 and 1-3 servings per week of mushrooms was associated with a lower risk of all-cause mortality (HR = 0.864, 95% CI = 0.784-0.952; HR = 0.869, 95% CI = 0.771-0.980) than non-consumption. This prospective cohort study demonstrated that low and medium mushroom consumption is associated with a lower risk of all-cause mortality in men and women. However, only men who consumed <1 and 1-3 servings per week of mushrooms exhibited a lower risk of CVD mortality.

Transverse myelitis caused by herpes zoster following COVID-19 vaccination: A case report.

BACKGROUND: Transverse myelitis (TM) is characterized by sudden lower extremity progressive weakness and sensory impairment, and most patients have a history of advanced viral infection symptoms. A variety of disorders can cause TM in association with viral or nonviral infection, vascular, neoplasia, collagen vascular, and iatrogenic, such as vaccination. Vaccination has become common through the global implementation against coronavirus disease 2019 (COVID-19) and reported complications like herpes zoster (HZ) activation has increased. CASE SUMMARY: This is a 68-year-old woman who developed multiple pustules and scabs at the T6-T9 dermatome site 1 wk after vaccination with the COVID-19 vaccine (Oxford/AstraZeneca ([ChAdOx1S{recombinant}]). The patient had a paraplegia aggravation 3 wk after HZ symptoms started. Spinal magnetic resonance imaging (MRI) showed transverse myelitis at the T6-T9 Level. Treatment was acyclovir with steroids combined with physical therapy. Her neurological function was slowly restored by Day 17. CONCLUSION: HZ developed after COVID-19 vaccination, which may lead to more severe complications. Therefore, HZ treatment itself should not be delayed. If neurological complications worsen after appropriate management, an immediate diagnostic procedure, such as magnetic resonance imaging and laboratory tests, will start and should treat the neurological complications.

Sex-specific effects of a high fat diet on aortic inflammation and dysfunction.

Obesity and vascular dysfunction are independent and sexually dimorphic risk factors for cardiovascular disease. A high fat diet (HFD) is often used to model obesity in mice, but the sex-specific effects of this diet on aortic inflammation and function are unclear. Therefore, we characterized the aortic immune cell profile and function in 6-week-old male and female C57BL/6 mice fed a normal chow diet (NCD) or HFD for 10 weeks. Metabolic parameters were measured weekly and fortnightly. At end point, aortic immune cell populations and endothelial function were characterized using flow cytometry and wire myography. HFD-male mice had higher bodyweight, blood cholesterol, fasting blood glucose and plasma insulin levels than NCD mice (P < 0.05). HFD did not alter systolic blood pressure (SBP), glycated hemoglobin or blood triglycerides in either sex. HFD-females had delayed increases in bodyweight with a transient increase in fasting blood glucose at week 8 (P < 0.05). Flow cytometry revealed fewer proinflammatory aortic monocytes in females fed a HFD compared to NCD. HFD did not affect aortic leukocyte populations in males. Conversely, HFD impaired endothelium-dependent vasorelaxation, but only in males. Overall, this highlights biological sex as a key factor determining vascular disease severity in HFD-fed mice.

Comparison of blood pressure and sympathetic activity of rabbits in their home cage and the laboratory environment.

Methodological improvements in measuring cardiovascular parameters have meant that data can be collected from freely moving animals in their home cage. However, experiments in rabbits still often require them to be restrained in a laboratory setting. The aim of this study was to determine whether measurements collected when rabbits were placed in a holding box in the laboratory are representative of values obtained in freely moving conscious rabbits. Nine New Zealand White rabbits received two radiotelemetry implants to monitor mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). The MAP measured in the laboratory (71 ± 1 mmHg) was similar to that in the home cage (69 ± 1 mmHg), but there was less MAP variability. The RSNA was also similar in both environments. In contrast, laboratory heart rate (HR) was 7% lower than home cage HR (181 ± 4 beats min(-1), P < 0.001), but HR variability was similar. Baroreflex gain, assessed by spectral analysis, was 19% higher in the laboratory than in the home cage due to lower MAP mid-frequency variability in the laboratory. Home cage circadian patterns of MAP and HR were strongly influenced by feeding and activity. Nevertheless, MAP and RSNA laboratory measurements were the same as average 24 h values and remained similar over several weeks. We conclude that while HR is generally lower in the laboratory, a valid representation of MAP and RSNA can be given by laboratory measurements.

Intrauterine growth restriction coupled with hyperglycemia: effects on cardiac structure in adult rats.

BACKGROUND: Intrauterine growth restriction (IUGR) has been linked to heart disease in adulthood. Hence the IUGR heart is likely to be vulnerable to diabetic heart disease. The aim of this study was to examine the effect of induction of type 1 diabetes on myocardial collagen deposition and cardiac function in adult rats with a history of IUGR, after controlling blood glucose levels. METHODS: IUGR was induced by protein restriction in the pregnant female rat. When the offspring were 24 wk of age, diabetes was induced in male IUGR and non-IUGR rats by means of streptozotocin; insulin injections were used to maintain blood glucose levels at a mild (7-10 mmol/l; n = 8 per group) or moderate level (10-15 mmol/l; n = 8 per group). Echocardiography and cardiac morphology analyses were carried out when the rats were 32 wk of age. RESULTS: IUGR offspring exhibited cardiac hypertrophy at 32 wk, including a thicker posterior wall and increased interstitial fibrosis in the left ventricle. Hyperglycemia led to an increase in heart size and myocardial fibrosis. The response to hyperglycemia was not different between IUGR and non-IUGR rats; however, cardiac fibrosis was greatest when diabetes was present along with a history of IUGR. In general, maintaining blood glucose levels at a mildly hyperglycemic level attenuated the adverse effects of hyperglycemia but did not reverse the fibrosis. CONCLUSION: Exacerbated fibrosis in hyperglycemic hearts of IUGR offspring may lead to long-term cardiac dysfunction.

Dairy product consumption and type 2 diabetes among Korean adults: a prospective cohort study based on the Health Examinees (HEXA) study.

OBJECTIVES: It has been suggested that the consumption of dairy products helps lower the prevalence of type 2 diabetes (T2D). We investigated the association between the consumption of dairy products and T2D events in middle-aged Korean adults. METHODS: We followed up 53,288 participants (16,895 male and 36,393 female) in the Health Examinees (HEXA) study. The consumption of dairy products was assessed using the self-administered food frequency questionnaire, and T2D was defined according to the 2015 treatment guidelines of the Korean Diabetes Association. Hazard ratios (HRs) and 95% confidence intervals (CIs) between the consumption of dairy products and the risk of T2D were calculated using Cox proportional hazards models after adjusting for potential confounders. Spline regression was used to better represent the association between the consumption of dairy products and the risk of T2D. RESULTS: Among male, those with higher consumption of dairy products had a significantly lower risk of T2D than those who consumed essentially no dairy products (HR, 0.73; 95% CI, 0.58 to 0.91). In particular, consumption of yogurt (HR, 0.75; 95% CI, 0.60 to 0.93; ptrend=0.035) and cheese (HR, 0.66; 95% CI, 0.49 to 0.89; ptrend=0.005) was negatively associated with the incidence of T2D in male. In female, daily consumption of 1 serving of yogurt decreased the risk of T2D by 11%. CONCLUSIONS: The association between the consumption of dairy products and the risk of T2D differed by sex and dairy product type. Further prospective studies are needed to confirm these associations.

The association between fruit and vegetable consumption and metabolic syndrome in Korean adults: does multivitamin use matter?

OBJECTIVES: Metabolic syndrome (MetS) is closely associated with dietary intake; however, few studies have investigated whether the consumption of fruits and vegetables and multivitamin use affect MetS in the Korean population. This study aimed to examine these effects in Korean adults. METHODS: This was a cross-sectional study of 89,548 participants aged between 40 years and 69 years selected from the baseline data of the Health Examinees study conducted in Korea. Fresh vegetable and fruit consumption was assessed using a validated 106-item food frequency questionnaire. MetS and its components were defined using the National Cholesterol Education Program, Adult Treatment Panel III criteria. Multivariate logistic regression analyses were conducted to identify associations of fresh vegetable, fruit, and fresh vegetable+fruit consumption and multivitamin use with the prevalence of MetS. RESULTS: Female in the highest quartile of fresh vegetable, fruit, and fresh vegetable + fruit consumption exhibited a lower prevalence of MetS than those in the lowest quartile. An inverse association with the prevalence of MetS was observed among male with only fresh vegetable consumption. The interaction between the 3 categories and multivitamin intake on the prevalence of MetS was not significant (all pinteraction>0.05), regardless of sex. CONCLUSIONS: Multivitamin use and consumption of fresh vegetables and fruits had no significant synergistic effects. Although fresh vegetable and fruit consumption showed an inverse association with the prevalence of MetS, this relationship was not altered by multivitamin use.

Induction of hyperglycemia in adult intrauterine growth-restricted rats: effects on renal function.

Intrauterine growth restriction (IUGR) leads to a reduction in nephron endowment at birth and is linked to renal dysfunction in adulthood. The aim of the present study was to determine whether kidneys of IUGR rat offspring are more vulnerable to a secondary insult of hyperglycemia. IUGR was induced in Wistar-Kyoto rats by maternal protein restriction. At 24 wk of age, diabetes was induced in male IUGR and non-IUGR offspring by streptozotocin injection; insulin was injected daily to maintain blood glucose levels at either a mild (7-10 mmol/l; n=8/group) or a moderate (10-15 mmol/l; n=8/group) level. At 32 wk of age, renal function was assessed using ultrasound and [(3)H]inulin and [(14)C]para-aminohippurate clearance techniques. Conscious mean arterial blood pressure and heart rate were unchanged in IUGR offspring. Relative kidney length was increased significantly in IUGR offspring, and renal function was altered significantly; of importance, there was a significant increase in filtration fraction, indicative of glomerular hyperfiltration. Induction of hyperglycemia led to marked impairment of renal function. However, the response to hyperglycemia was not different between IUGR and non-IUGR offspring. Maintaining blood glucose levels at a mild hyperglycemic level led to marked improvement in all measures of renal function in IUGR and non-IUGR offspring. In conclusion, while the IUGR offspring showed evidence of hyperfiltration, the response to hyperglycemia was similar in IUGR and non-IUGR kidneys in adulthood. Importantly, maintaining blood glucose levels at a mild hyperglycemic level markedly attenuated the renal dysfunction associated with diabetes, even in IUGR offspring.

IUGR in the absence of postnatal "catch-up" growth leads to improved whole body insulin sensitivity in rat offspring.

A suboptimal in utero environment leads to fetal adaptations to ensure short-term survival but in the long-term may lead to disease when the postnatal growth does not reflect that in utero. This study examined the effect of IUGR on whole body insulin sensitivity and metabolic activity in adult rats. Female Wistar-Kyoto rats were fed either a normal protein diet (NPD 20% casein) or a low protein diet (LPD; 8.7% casein) during pregnancy and 2 wk of lactation. In offspring at 32 wk of age, indirect calorimetry and dual energy x-ray absorptiometry (DEXA) were performed to assess metabolic activity and body composition. Insulin sensitivity was assessed using a euglycemic-hyperinsulinemic clamp. At 3 d of age, male and female LPD offspring were 23 and 27% smaller than controls, respectively. They remained significantly smaller throughout the experimental period (∼10% smaller at 32 wk). Importantly, there was increased insulin sensitivity in LPD offspring (47% increase in males and 38% increase in females); pancreatic insulin content was normal. Body composition, O2 consumption, respiratory exchange ratio (RER), and locomotor activity were not different to controls. These findings suggest that in the absence of "catch-up" growth IUGR programs for improved insulin sensitivity.

Metabolically healthy obesity and the risk of all-cause and cardiovascular disease mortality in a Korean population: a prospective cohort study.

OBJECTIVES: This study aimed to examine the association between metabolically healthy obesity and all-cause and cardiovascular disease (CVD) mortality in a Korean population. DESIGN: A prospective study. SETTING: This study used data from the Korean Genome and Epidemiology Study. PARTICIPANTS: A total of 140 137 participants were followed up over a median period of 9.2 years. Participants were categorised into four groups according to obesity (obese: body mass index ≥25 kg/m2 or non-obese) and metabolic health (metabolically unhealthy: two or more metabolic abnormalities or metabolically healthy). PRIMARY AND SECONDARY OUTCOME MEASURES: All-cause and CVD mortality of the participants until 31 December 2018 were ascertained by the National Health Insurance Service of beneficiary status of Korea. RESULTS: Metabolically unhealthy non-obese participants were at elevated risk of all-cause mortality (HR, 1.12; 95% CI, 1.04 to 1.21; p=0.0019) and CVD mortality (HR, 1.39; 95% CI, 1.17 to 1.65; p=0.0002), particularly mortality from ischaemic heart disease (IHD) (HR, 1.54; 95% CI, 1.10 to 2.14; p=0.0116) compared with metabolically healthy non-obese participants. Surprisingly, metabolically healthy obese participants were at reduced risk of all-cause mortality (HR, 0.89; 95% CI, 0.81 to 0.98; p=0.0197). Metabolically unhealthy obese participants were at elevated risk of CVD mortality (HR, 1.51; 95% CI, 1.26 to 1.81; p<0.0001) and IHD mortality (HR, 1.88; 95% CI, 1.35 to 2.63; p=0.0002) compared with metabolically healthy non-obese participants. CONCLUSIONS: In a Korean population, metabolically healthy obese participants had reduced risk of all-cause mortality compared with their non-obese counterparts, whereas metabolically unhealthy participants had elevated risk of CVD mortality, in particular mortality from IHD regardless of obesity.