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Phenolic-rich plant extracts have been demonstrated to improve glycemic control in individuals with prediabetes. However, there is increasing evidence that people with prediabetes are not a homogeneous group but exhibit different glycemic profiles leading to the existence of prediabetes subgroups. Prediabetes subgroups have been identified as: isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), and combined impaired fasting glucose and glucose intolerance (IFG/IGT). The present review investigates human clinical trials examining the hypoglycemic potential of phenolic-rich plant extracts in prediabetes and prediabetes subgroups. Artemisia princeps Pampanini, soy (Glycine max (L.) Merrill) leaf and Citrus junos Tanaka peel have been demonstrated to improve fasting glycemia and thus may be more useful for individuals with IFG with increasing hepatic insulin resistance. In contrast, white mulberry (Morus alba Linn.) leaf, persimmon (Diospyros kaki) leaf and Acacia. Mearnsii bark were shown to improve postprandial glycemia and hence may be preferably beneficial for individuals with IGT with increasing muscle insulin resistance. Elaeis guineensis leaf was observed to improve both fasting and postprandial glycemic measures depending on the dose. Current evidence remains scarce regarding the impact of the plant extracts on glycemic control in prediabetes subgroups and therefore warrants further study.

Background: Plant extracts may help to improve glycemic control in individuals with poor glycemic control. However, few studies have been investigated in the prediabetes cohort, which is a high-risk condition for T2DM. Thus, this study aimed to investigate the acute effect of grape seed, rooibos tea, and olive leaf extracts on postprandial blood glucose and insulin in participants with prediabetes. Methods: An acute, single-blind, placebo-controlled, non-randomized, crossover study (ACTRN12617000837325) where placebo and extracts of grape seed, rooibos tea and olive leaf standardized for total antioxidant capacity were given separately during an oral glucose tolerance test to participants (n=19, five men and fourteen women, aged 65.0 ± 1.6 years, Body Mass Index (BMI) 27.3 ± 1.1 kg/m 2 ) with prediabetes (Glycated hemoglobin A1c (HbA1c) 42 ± 1 mmol/mol). The primary outcome incremental area under the curve of glucose (iAUC glucose ) was examined with other glycemic measures. Data was analyzed using linear mixed model for repeated measures. Secondary analysis was conducted by stratifying participants into either a healthier or less healthy subgroup based on the postprandial time to glucose and insulin peaks, with the less healthy subgroup experiencing delayed glucose and/or insulin peaks. Results: There were no overall significant changes to glucose and insulin measures between all plant extracts and placebo ( p >0.05). Upon secondary analysis, all extracts affected glycemic responses in the less healthy subgroup. Compared to placebo, grape seed reduced plasma iAUC glucose ( p =0.016, 21.9% reduction), 2 h postprandial glucose (2hPG) ( p =0.034, 14.7% reduction) and metabolic clearance rate of glucose (MCR glucose ) ( p =0.016, 16.7% increase). It also improved insulin indices such as 2 h postprandial insulin (2hPI) ( p =0.029, 22.4% reduction) and Stumvoll overall insulin sensitivity index (ISI overall ) ( p =0.028, 15.0% increase). Rooibos tea extract significantly improved β-cell function as demonstrated by the increased oral disposition index (DI) ( p =0.031, 32.4% increase) compared to placebo. Olive leaf extract significantly increased incremental area under the curve of insulin (iAUC insulin ) ( p =0.040, 16.7% increase). Conclusion: Grape seed, rooibos tea and olive leaf extracts demonstrated acute hypoglycemic benefits in adults with prediabetes and having less healthy metabolic profiles. A chronic study on the plant extracts is warranted to determine their longer-term impact on prediabetes. Trial Registration ID: ACTRN12617000837325 Keywords: grape seed extract; rooibos tea extract; olive leaf extract; impaired glycemic control; hyperglycemia; hypoglycemic effects; insulin sensitivity; beta-cell function

Increasing fruit and vegetable consumption is a key lifestyle modification in the prevention and treatment of hypertension. Kiwifruit has previously been shown to have favorable effects on blood pressure (BP), likely through inhibiting angiotensin I-converting enzyme activity. We hypothesized that the replacement of 2 fruit servings in a healthy diet with 2 green kiwifruit a day would significantly improve BP and other markers of cardiovascular function, including heart rate, stroke volume, cardiac output, and total peripheral resistance, in a group of hypercholesterolemic men. Using a controlled cross-over study design, 85 subjects completed a 4-week healthy diet run-in period before randomization to one of two 4-week intervention sequences in which they either consumed 2 green kiwifruit a day plus a healthy diet (intervention) or consumed a healthy diet alone (control). Blood pressure and other measures of cardiovascular function (using a Finometer MIDI [Finapres Medical Systems B.V, Amsterdam, The Netherlands] and standard oscillometric device) and anthropometric measurements were taken before and at the end of the treatment periods. A physical activity questionnaire was completed during the last visit. Subjects were found to be predominantly normotensive (43.5%) or prehypertensive (50.6%) and quite physically active (>30 minutes of moderate to vigorous physical activity/day in >80% subjects). No significant differences were seen for BP or any of the other markers, including heart rate, stroke volume, cardiac output, and total peripheral resistance. In conclusion, in this hypercholesterolemic, nonhypertensive group, no beneficial effects on BP or other markers of cardiovascular function were seen when consuming 2 kiwifruit a day against the background of a healthy diet.

Kiwifruit has the potential to improve markers of metabolic dysfunction, but the response may be influenced by inflammatory state. We aimed to investigate whether inflammatory state would modulate the effect of consuming two green kiwifruit daily on plasma lipids and markers of inflammation.Eighty-five hypercholesterolaemic men completed a 4-week healthy diet run-in, before randomisation to a controlled cross-over study of two 4-week interventions of two green kiwifruit/day plus healthy diet (intervention) or healthy diet alone (control). Anthropometric measures and fasting blood samples (plasma lipids, serum apolipoproteins A1 and B, high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, tumour necrosis factor-alpha (TNF-α) and IL-10) were taken at baseline, 4 and 8 weeks. Subjects were divided into low and medium inflammatory groups, using pre-intervention hs-CRP concentrations (hs-CRP1 and 1-3 mg/L, respectively). In the medium inflammatory group the kiwifruit intervention resulted in significant improvements in plasma high-density lipoprotein cholesterol (HDL-C) (mean difference 0.08 [95% CI: 0.03, 0.12] mmol/L [P0.001]), total cholesterol (TC)/HDL-C ratio (-0.29 [-0.45, -0.14] mmol/L [P = 0.001]), plasma hs-CRP (-22.1 [-33.6, -4.97]% [P = 0.01]) and IL-6 (-43.7 [-63.0, -14.1]% [P = 0.01]) compared to control treatment. No effects were seen in the low inflammatory group. There were significant between inflammation group differences for TC/HDL-C (P = 0.02), triglyceride (TG)/HDL-C (P = 0.05), and plasma IL-6 (P = 0.04).Inflammatory state modulated responses to the kiwifruit intervention by improving inflammatory markers and lipid profiles in subjects with modestly elevated CRP, suggesting this group may particularly benefit from the regular consumption of green kiwifruit. Registered 16th March 2010, Australian New Zealand Clinical Trials Registry (no. ACTRN12610000213044), www.ANZCTR.org.au.

Fruit and vegetables are key elements of a cardioprotective diet, but benefits on plasma lipids, especially HDL-cholesterol (HDL-C), are inconsistent both within and between studies. In the present study, we investigated whether four selected HDL-C-related polymorphisms (cholesteryl ester transfer protein (CETP) Taq1B, APOA1 − 75G/A, hepatic lipase (LIPC) − 514C → T, and endothelial lipase (LIPG) I24582) modulate the plasma lipid response to a kiwifruit intervention. This is a retrospective analysis of data collected during a 12-week randomised controlled cross-over trial. A total of eighty-five hypercholesterolaemic men completed a 4-week healthy diet run-in period before being randomised to one of two 4-week intervention sequences of two green kiwifruit/d plus healthy diet (kiwifruit intervention) or healthy diet alone (control intervention). The measurement of anthropometric parameters and collection of fasting blood samples were carried out at baseline 1 and after the run-in (baseline 2) and intervention periods. At baseline 2, B1/B1 homozygotes of the CETPTaq1B gene had significantly higher total cholesterol:HDL-C, TAG:HDL-C, and apoB:apoA1 ratios and small-dense LDL concentrations than B2 carriers. A significant CETP Taq1B genotype × intervention interaction was observed for the TAG:HDL-C ratio (P= 0·03). B1/B1 homozygotes had a significantly lower TAG:HDL-C ( − 0·23 (sd 0·58) mmol/l; P= 0·03) ratio after the kiwifruit intervention than after the control intervention, whereas the ratio of B2 carriers was not affected. The lipid response was not affected by other gene polymorphisms. In conclusion, the significant decrease in the TAG:HDL-C ratio in B1/B1 homozygotes suggests that regular inclusion of green kiwifruit as part of a healthy diet may improve the lipid profiles of hypercholesterolaemic men with this genotype.

The unique composition of green kiwifruit has the potential to benefit CVD risk. The aim of the present study was to investigate the effect of consuming two green kiwifruits daily in conjunction with a healthy diet on plasma lipids and other metabolic markers and to examine response according toAPOEgenotype in hypercholesterolaemic men. After undergoing a 4-week healthy diet, eighty-five hypercholesterolaemic men (LDL-cholesterol (LDL-C) >3·0 mmol/l and TAG P= 0·004) and the total cholesterol (TC):HDL-C ratio was significantly lower (mean difference − 0·15; 95 % CI − 0·24, − 0·05 mmol/l;P= 0·002) compared with the control. In carriers of theAPOE4allele, TAG decreased significantly (mean difference − 0·18; 95 % CI − 0·34, − 0·02 mmol/l;P= 0·03) with kiwifruit compared with control. There were no significant differences between the two interventions for plasma TC, LDL-C, insulin, glucose, hs-CRP and BP. The small but significant increase in HDL-C and decrease in TC:HDL-C ratio and TAG (inAPOE4carriers) suggest that the regular inclusion of green kiwifruit as part of a healthy diet may be beneficial in improving the lipid profiles of men with high cholesterol.

Asian Indians are an at-risk group for vitamin B12 deficiency (because of vegetarianism) and insulin resistance (IR). Vegetarianism and consequent vitamin B12 deficiency may be associated with IR. This study aimed to describe the vitamin B12 status of predominantly overweight/obese women of South Asian origin living in Auckland and to correlate serum vitamin B12 and vegetarian status with IR as part of the larger Surya Study looking at health and lifestyle in this population.This was a cross-sectional study of 135 women at least 20 y of age who were not taking vitamin B supplements or medications that could affect vitamin B12 concentrations (serum vitamin B12800 pmol/L). Data collection included serum vitamin B12, serum folate, measurements of IR (HOMA2-IR), and anthropometry. Vegetarian status was established for 124 subjects (90 non-vegetarians, 34 vegetarians).Mean serum vitamin B12 was 227 pmol/L (95% confidence interval 210-245), serum folate was 19.1 nmol/L (18.0-20.2), and HOMA2-IR was 1.24 (1.13-1.36). Non-vegetarians had higher serum vitamin B12 levels (257 pmol/L, 235-281) than vegetarians (181 pmol/L, 159-207), P0.001. Vitamin B12 deficiency (150 pmol/L) in vegetarians was 24% versus 9% in non-vegetarians. Non-vegetarians had increased body mass index (25.9 kg/m², 25.0-26.9, versus 23.9 kg/m², 22.6-25.3), waist circumference (81 ± 10.1 versus 75.8 ± 9.88 cm), and HOMA2-IR levels (1.30, 1.17-1.46, versus 1.00, 0.83-1.22). No correlation was found between serum vitamin B12 and HOMA2-IR. A significant positive correlation between non-vegetarian status and IR disappeared after controlling for body mass index.This study population has a low serum vitamin B12 status, especially if vegetarian. The high rates of observed obesity may have overshadowed any other contributing factor to IR.