Lower carbohydrate and higher fat intakes are associated with higher hemoglobin A1c: findings from the UK National Diet and Nutrition Survey 2008–2016

Diabetes prevalence is predicted to rise from 425 million people in 2017 to 629 million people by 2045 [1]. It is clear that body fat accumulation is the dominant factor behind development of type 2 diabetes mellitus (T2DM), and consistent evidence shows that reversing that process by weight loss is the key mechanism for prevention, as well as for remission of established T2DM [2]. Several large diabetes prevention trials have shown modest weight loss to be effective, principally by lowering fat intake (< 30%E) along with lifestyle modification [3‐6].

It has been hypothesized that lower postprandial glucose excursion on a low-carbohydrate, high-fat (LCHF) diet may lead to a better glucose control [7, 8]. LCHF diets have been promoted as a possible strategy for the management and prevention of T2DM, but there is no consensus on the best macronutrient composition [9]. LCHF diets can certainly lead to weight loss and reduce HbA1c, but there is no clear evidence of LCHF diet superiority over other dietary approaches, with most of meta-analyses of low to moderate methodological quality [10‐13]. Furthermore, there are indications that carbohydrate-restricted diets may not provide the full complement of micronutrients leading to potential insufficiencies in vitamins and minerals [14].

Longitudinal cohort studies have not shown conclusive associations between LCHF diets and long-term risk of T2DM [15‐17]. No LCHF diet trial (whether or not as part of a wider lifestyle modification) has yet been conducted aiming to prevent incident T2DM [18].

The present study was conducted using the National Diet and Nutrition Survey (NDNS), the largest UK database of a continuous, cross-sectional survey for nutrition and health, using prospective dietary records and providing information on biomarkers. It investigated the relationships of reported dietary carbohydrate, fat, saturated fat, LCHF dietary patterns and adherence to dietary recommendations with HbA1c concentration (as a marker of diabetes and heart disease risks) and with risk of T2DM.

Table 1 shows population characteristics. Between 2008 and 2016, a total of 3234 participants (mean age 46.3 ± 18.5 years, 42.6% men) had complete data and were included in the analysis. Of these, 104 participants (3.2%) had a known diagnosis of diabetes. Among those without a diabetes diagnosis (n = 3130), mean HbA1c was 5.5 ± 0.5%, n = 90 (2.8%) had HbA1c ≥ 6.5%, n = 365 (11.7%) had HbA1c ≥ 6.0%, and n = 1517 (48.5%) had an HbA1c ≥ 5.5%. Participants with either diabetes or HbA1c ≥ 5.5% were older (59 ± 14 and 54 ± 17 years, respectively) and had a higher BMI (32 ± 6 and 28 ± 5 kg/m², respectively) than those with lower HbA1c (age 38 ± 16 years, BMI 26 ± 5 kg/m²). Most participants were white (93.5%) and non-smokers (57.3%), and 12% were following self-reported weight-loss diets (Table 1).

Dietary intakes were comparable across groups of diagnosed and non-diagnosed diabetes (Table 1). Mean total energy intake was 1815 ± 551 kcal. Carbohydrate, fat, saturated fat and protein intakes were approximately 48%, 35%, 13% and 17% food energy across all groups. Non-starch polysaccharides intake was low at 13.7 ± 5 g/day (target 18 g/day, Englyst method). Participants who reported being on a weight-loss diet had higher fruits and vegetables intakes (317 ± 203 g/day) than the overall sample population (277 ± 172 g/day), with no difference in LCHF or DRV scores. The distributions of the LCHF and DRV scores are shown in Online Resource Fig. 1. There was a negative correlation between LCHF and DRV scores (rho = − 0.63, P < 0.001).

There has been very limited evidence supporting the use of LCHF diets for the prevention of T2DM. To our knowledge, this is the first study investigating whether carbohydrate intake and LCHF dietary pattern relate to HbA1c concentration in a population-based cross-sectional study of nutrition and health. Surprisingly, given the enthusiasm for LCHF diets in the media and from some professional commentators, we found that lower carbohydrate intake was associated with significantly greater odds of T2DM and higher HbA1c concentration. Higher adherence to conventional dietary recommendations (basing meals on starchy carbohydrates, lower fat and saturated fat contents, eating more fruits and vegetables) was associated with lower HbA1c concentration.

Few longitudinal cohort studies have evaluated the links between LCHF diets and long-term risk of T2DM, with inconclusive findings [15, 16, 27]. The LCHF dietary pattern was associated with higher T2DM risk in men, women with history of gestational diabetes [15, 27], but another found no association in women without gestational diabetes [16]. A meta-analysis of four prospective studies with follow-up durations 3.6 to 20 years [28] showed no evidence of association between LCHF (highest quantile of LCHF score) and T2DM risk (pooled RR 1.17; 95% CI 0.90–1.51) but this small study had high heterogeneity (I² = 81.5%, P < 0.001). The authors did a subgroup analysis in those cohort studies with adjustment for total energy intake (n = 3 of 4) and found improvement in heterogeneity (pooled RR 1.32; 95% CI 1.05–1.75; I² = 0%) [28]. All included studies (n = 4) were assessed as Newcastle–Ottawa Scale ≥5 for methodological quality, but a subgroup analysis by study quality (score > 7 and ≤7) revealed an association only in lower-quality studies (score ≤7; n = 2/4; pooled RR 1.31; 95% CI 1.15–1.50; I² = 0%), with no association in two higher quality studies (score > 7; pooled RR 1.09; 95% CI: 0.73–1.63; I² = 86%) [28]. The evidence on this topic is clearly scarce and varies in quality, and dietary assessment quality is a limiting factor. All prospective studies used food frequency questionnaires for dietary assessment, which are less reliable than the 4-day food diary used in the UK NDNS survey. While cross sectional in nature, our study and indings link LCHF diets to both T2DM and HbA1c level, and therefore add to the findings of previous cohort studies.

A beneficial relationship between adherence to dietary recommendations and lower HbA1c and T2DM risk is reassuring, and in keeping with previous literature. Another recent UK cross-sectional study showed similarly that adherence to UK dietary guidelines was associated with lower HbA1c and T2DM risk [23]. Also, findings from prospective studies showed that adherence to dietary guidelines, increased fruits and vegetables and whole grain intakes were associated with 7–30% lower risk of T2DM [29‐32]. Moreover, a secondary analysis of the Women’s Health Initiative Dietary Modification Trial showed that low-fat diet, with increased grains, fruits and vegetables, reduced the rate of conversion from normoglycemia to impaired fasting glucose by 25% after 8-year intervention [4]. Notably, participants in this trial increased carbohydrate intake by ~ 8% of energy, with a corresponding reciprocal decrease in fat intake of ~ 8%. This also supports the assertion that greater carbohydrate intake, particularly from grains and fruits, could delay progression to T2DM [4].

Other mechanisms (e.g., oxidative stress, peripheral insulin resistance), aside from carbohydrates intake and postprandial glycemia, may contribute to elevation of HbA1c and might explain the association with lower carbohydrate diets. Avoiding carbohydrate foods like whole grains, fruits and some starchy vegetables inevitably lowers micronutrients and bioactive compounds, fiber, and some minerals (e.g., magnesium) [14]. Lower fruits and associated nutrients and bioactives, alongside higher fat intake, could impact on oxidative stress [33‐37]. High oxidative stress consequently enhances protein glycation, including the formation of fructosamine and HbA1c. Vlassopoulos et al. modelled that under normal glucose concentration, higher oxidative stress increases fructosamine production by 35%, compared to non-oxidative state [38].

Oxidative stress, as well low magnesium status and high fatty acids concentration (from high-fat intake), also raises insulin resistance through an alteration in the insulin receptor signaling pathway [39, 40]. A recent well-controlled crossover isocaloric feeding study in adults with overweight/obesity reported a decline in insulin sensitivity, reduction in glucose disposal rate by − 0.37 ± 0.15 mmol/min measured by hyperinsulinemic-euglycemic clamp, after 4 weeks of high-fat/high-saturated fat diet compared to a low-fat diet (glucose disposal rate + 0.12 ± 0.11 mmol/min, P < 0.01) [41]. All factors discussed above together with chronic inflammatory state in obesity could explain the associations between LCHF diet, high saturated fat intake and high HbA1c that were robust in a subgroup of individuals with BMI ≥ 25 kg/m². Consistently, recent meta-analyses have shown that low magnesium intake was associated with higher risk of T2DM by 17–22% [42, 43].

This study has limitations that must be considered when evaluating its findings. This study could not refer to very low-carbohydrate ketogenic diets, as there are no data on ketosis status for this dataset. Notably, there is no standardized definition of LCHF diets, although < 26%E CHO has been proposed as a cut-off value [44]. Only 0.24% of the study sample (n = 8/3234) consumed carbohydrates below this threshold, a finding comparable to data from the UK Biobank (0.34% of participants) [45]. As with all cross-sectional studies, residual confounders and reverse causation could not be excluded; for example, the association between low-carbohydrate intake and T2DM prevalence could be explained by that those with diabetes might have changed their dietary behaviour by reducing carbohydrate intake. We, therefore, conducted analyses in a population mainly without diabetes, including in-depth sensitivity analyses and used a biomarker (HbA1c) as an outcome to minimize bias. The LCHF score is arbitrary. However, this score allows a practical approach to assess dietary pattern, reflecting the complementarity of food/nutrient intakes rather than focusing on single nutrients that are never consumed in isolation [46]. Finally, we could not distinguish between type 1 and type 2 diabetes, including those with insulin use, in the present study. However, the prevalence of type 1 diabetes is approximately 0.6% of UK population (about 10% of people with diabetes in the UK [26]); any individuals with type 1 diabetes in the sample could have little impact on our analyses, as shown through exclusion simulations in our sensitivity analyses.

A key strength of our study is its use of the UK nationally representative data for hypothesis testing on a topic of substantial scientific and public interest. Results could, therefore, be generalizable to the UK population and possibly to other countries, as dietary recommendations (to eat more whole grain, fruits and vegetables, and lower fat, saturated fat, sodium and sugar) are rather similar across many countries [47, 48]. Using prospective dietary records does not rely on memory so may provide more accurate estimates of actual intakes than food frequency questionnaires.

Regarding diabetes prevention, our cross-sectional results oppose the simplistic notion that lower carbohydrate contents in the diet per se could lower HbA1c concentration, particularly in people without diagnosed diabetes. Long-term, high-quality randomized controlled trials of LCHF diets on diabetes prevention are needed before such diets should be recommended.