Adhering to UK Dietary Fat Recommendations Reduces Risk of Type 2 Diabetes

Diabetes is the fastest growing health threat in the UK, with it being estimated that 5 million people in the UK will suffer by 2025 [1], yet it is well known that making lifestyle changes can delay or prevent onset of type 2 diabetes. A recent study conducted by von Frankenberg et al. suggested that adhering to a high fat diet decreases insulin sensitivity in obese and overweight individuals, and that this could be associated with increased risk of type 2 diabetes [2]. From discussing this conclusion within the wider literature, it has been concluded that a diet adhering to UK recommendations, with 35% of energy intake from fat and no more than 11% from saturated fat, without excess daily energy intake, may be the most practical dietary advice to give to reduce risk of type 2 diabetes within the general population.

Non-insulin dependent, or type 2, diabetes mellitus is considered one of the most common global chronic health problems and accounts for 90% of all cases of diabetes in the UK [3]. The metabolic disorder is often described as ‘starvation in the midst of plenty’; this is that extracellular glucose concentration may be high yet the intracellular levels are low [4]. The characteristic persistent elevation of blood glucose concentration can lead to debilitating or life threatening complications including kidney disease, diabetic retinopathy, nerve damage and increased risk of CHD or stroke [5].

Insulin secretion from pancreatic beta cells is induced by a postprandial rise in blood glucose concentration. It is transported to muscle and liver cells to stimulate glucose uptake from the bloodstream for storage as glycogen, and to inhibit liver gluconeogenesis [6]. In those with type 2 diabetes cells are resistant to the effects of insulin, resulting in glucose remaining in the blood stream. Compensatory insulin production occurs, with the subsequent suppression of GLUT4 production on cell membranes, further reducing glucose transport [7]. Prolonged upregulation of insulin secretion can ultimately lead to beta cell dysfunction [8], with poor blood glucose control.

The true cause of insulin resistance is not confirmed however, unlike the autoimmune type 1 form, appropriate lifestyle choices, including consuming a healthy diet and participating in regular exercise, are believed to prevent or delay onset of type 2 diabetes [9]. It is often considered a lipid disorder due to the frequent associations found with high levels of plasma free fatty acids (FFA) [10]. Although this state is often attributed to obesity, FFA levels are also elevated after a fat rich meal [11]. A recently published study by von Frankenberg et al. investigated the association between the fat content of the diet and insulin sensitivity in overweight and obese individuals with normal glucose tolerance [2]. This review will discuss their conclusions within the wider research to determine whether a high fat diet may contribute to an increased risk of type 2 diabetes independent of weight loss.

Method

Study population

Men and women aged 18-55 years were included in the study with BMI >27kg/m², normal fasting blood glucose tolerance of <5mmol/L and 2 hour glucose of <7.8mmol/L.

Dietary intervention

Subjects followed a 10-day control diet then 4 weeks on a low fat diet (LFD) or high fat diet (HFD). Six subjects were randomised to complete either the LFD or HFD, and seven subjects completed both diets with a 6 week wash out period and 10-day control diet in between.

All food was provided throughout the interventions and subjects were instructed to record all foods consumed, returning anything left for measurement. The control diet had 35% energy from fat (12% SFA), 47% energy from CHO and 18% energy from protein. The LFD had 20% energy from fat (8% SFA), 62% energy from CHO and 18% energy from protein. The HFD had 55% energy from fat (25% from SFA), 27% energy from CHO and 18% energy from protein. Main fat sources were butter and high oleic safflower oil. Fibre was standardised across the diets and fructose was limited to <30g/day in all three. Calorie intake was adjusted throughout the study to ensure weight remained stable.

Glucose measurements

At the end of the control and intervention diets insulin response and glucose tolerance were tested using an intravenous glucose tolerance test. Endogenous glucose production (EGP) and insulin sensitivity were estimated using the hyperinsulinemic-euglycemic clamp technique.

Fat distribution measurements

Dual-energy X-ray absorptiometry (DEXA) measured total fat and lean mass. Abdominal fat distribution and liver fat were measured using MRI and MRS abdominal images. Gradient ultracentrifugation isolated very low density lipoprotein (VLDL) fatty acids.

Calculations and statistical analysis

Glucose tolerance, reflected as the glucose disappearance constant (Kg), and the insulin response to glucose (AIRg) were calculated using the measurements form the intravenous glucose tolerance test, with insulin response being adjusted for insulin sensitivity to estimate beta-cell function. The rates of glucose appearance (Ra) and disappearance (Rd) were calculated using the clamp data based on the steady state achieved. EGP was found for the basal state and after the glucose infusion. Hepatic insulin sensitivity was based on the difference in the EGP values, as well as the hepatic insulin resistance (HIR) index.

Statistical analysis determined the association between the different diets and changes in the outcome variables. Significance of associations between changes in insulin sensitivity, abdominal fat distribution, adipokines and VLDL fatty acid composition were tested.

Results

Response to the LFD

Compared to the control diet, glucose tolerance increased significantly based on Kg despite little change in the AIRg. There was no significant change in insulin sensitivity as measured by Rd, HIR index, basal EGP or insulin-mediated suppression of EGP. There was no difference in fatty acid suppression.

A decrease in liver fat was observed but no significant change in intra-abdominal fat, subcutaneous fat or adipokines.

The proportion of stearic acid (18:0) and palmitic acid (16:0) in VLDL increased, as did palmitoleic acid (16:1 n-7), but linoleic acid (18:2 n-6) decreased.

Response to the HFD

Compared to the control diet, there was a significant decrease in Rd but no change in AIRg, Kg, HIR index, EGP or EGP suppression during the HFD, nor in the ability or insulin to suppress fatty acids.

No significant changes in intra-abdominal or liver fat were observed but subcutaneous fat increased significantly.

There was no change in the fatty acid composition of VLDL.

Comparison of the LFD and HFD

Comparing the changes from control in the LFD and HFD, the decrease in Rd on the HFD was significant, as was the increase in Kg on the LFD. The increase in subcutaneous fat on the HFD was also significant.

Changes in subcutaneous fat were positively associated with changes in Rd but there was no association with intra-abdominal fat, liver fat, adipokines, or the ratio of subcutaneous to intra-abdominal fat.

An increase in palmitic acid (16:0) in VLDL was positively associated with hepatic insulin resistance and changes in VLDL n-6 docosapentaenoic acid (22:5 n-6) were negatively associated with Rd.

Discussion

The study by von Frankenberg et al. found that consumption of a HFD, with 55% of energy obtained from fat, was associated with a decrease in insulin sensitivity during weight maintenance conditions [2]. Similar observations have been reported by Lovejoy et al. where adherence to a HFD containing 50% energy from fat decreased insulin sensitivity by 6% [12], and by Weigensberg et al. where a HFD in excess of 35% of energy as fat was associated with insulin resistance independent of body fat [13]. However, it has been suggested that the effects on insulin sensitivity may only be observed when calories from total fat exceeds the threshold of 35-40% of total daily intake [14], suggesting UK dietary recommendations of no more than 35% of energy from fat to be appropriate [15]. The decrease in insulin sensitivity may, however, be limited to muscle glucose uptake as von Frankenberg et al. found no effect of the HFD on hepatic insulin sensitivity [2], contrasting previous findings that excess hepatic diacylglycerols can cause insulin resistance and impair the activation of glycogen synthesis and inhibition of gluconeogenesis [16].

Despite the change in insulin sensitivity in the HFD group, there was no change in insulin sensitivity amongst those on the LFD, which may suggest that fat composition is of greater importance than total fat intake as the difference in saturated fat (SFA) content in the HFD compared to the control was significantly greater than the LFD (25% SFA in the HFD, 12% in the control and 8% in the LFD) [2]. The KANWU study found that insulin sensitivity was decreased by 10% on a high SFA diet. A positive association was also observed between long chain unsaturated fatty acid content of cell membranes and insulin sensitivity [17] due to their mediating effects on insulin receptor binding and affinity, ion permeability and cell signalling [14]. Similarly, increased insulin sensitivity has been observed in those following a high polyunsaturated fat (PUFA) diet compared to a high SFA diet [18], and the Nurses’ health study found n-6 PUFAs in particular to be linked to reduced risk of diabetes [19]. However, the effect of changing the fat composition of the diet may rely on also reducing total fat intake as it has been suggested that changes in insulin sensitivity in response to alterations in fat composition may not be seen in diets with fat intake beyond 37% of total energy [17].

Research also suggests that the isocaloric replacement of fat in the LFD with carbohydrates (CHO) in the von Frankenberg et al. study may have attenuated any beneficial effects on insulin sensitivity [14] due the stimulation of de novo lipogenesis in the liver by insulin. This may have accounted for the increase in palmitic, stearic and palmitoleic acid in VLDL [20]. The significance of this is that palmitic acid is the preferred substrate for ceramide synthesis, the levels of which are related to insulin resistance within muscles [10]. Although it may therefore be thought that a decrease in insulin sensitivity should have been observed by von Frankenberg et al. [2], however it was not, potentially due to the increase in palmitoleic acid reducing expression of pro-inflammatory genes and improving hepatic lipid metabolism [21].

Finally, visceral obesity is frequently associated with increased insulin resistance due to its lipolytic nature, delivering non-esterified fatty acids to the liver via the portal vein, and its ability to suppress adiponectin [22], which is usually related to increased insulin sensitivity by enhancing fat oxidation and inhibiting gluconeogenesis [23]. In contrast to the association between the increase in subcutaneous fat in the HFD group with insulin sensitivity [2] in the study by von Frankenberg et al., it has been suggested that there is a stronger inverse correlation between insulin sensitivity and intra-abdominal fat, for example Cnop et al. found intra-abdominal fat in lean insulin resistant subjects to be 70% greater than in lean insulin sensitive individuals [24]. This finding may be due to the closer negative association with adiponectin [25], suggesting it to be an intermediate between obesity and insulin resistance. A HFD could be thought to increase visceral obesity as as fat is said to act as a poor hunger cue [26] causing passive overconsumption of energy [27], however this is not likely to occur independent of weight gain. The weight stability of the subjects in the study by von Frankenberg et al. [2] may therefore have prevented an effect being observed, although the low CHO content of the HFD may have further contributed to the lack of change in intra-abdominal fat as Gower and Goss reported a low CHO diet to reduce intra-abdominal fat by 11% compared to a high CHO LFD [28].

Impacts

It would not be appropriate to generalise the conclusions obtained by von Frankenberg et al. to the wider population due to the small sample size of only 13 subjects being studied. However, after discussing this study within the findings from wider research, it could be stated that there is sufficient evidence to conclude that following a HFD may increase insulin resistance and a LFD should be recommended. To complement this, it may be beneficial to ensure dietary fat is primarily PUFA and MUFA as opposed to SFA to promote cell membrane fluidity and GLUT4 glucose transport [30]. It may be difficult for many individuals to lower daily fat intake to much below UK dietary recommendations, but the findings from the literature suggest that ensuring a favourable fatty acid composition in a diet at this fat intake is still likely to have beneficial effects on insulin sensitivity [17], consequently aiding blood glucose control, particularly in those that are overweight or obese, and reducing risk of developing type 2 diabetes.

Adherence to a LFD should not be taken as the sole recommendation for prevention or delay of type 2 diabetes onset. It has also been mentioned that high CHO intake may contribute to insulin resistance due to de novo lipogenesis [14], so it may also be essential to ensure excess CHO is not consumed, and that choices are primarily low glycaemic index for a slower rate of insulin secretion. Total energy intake is also of importance as a positive energy balance could increase intra-abdominal fat, which is strongly correlated with insulin resistance [24]. 

When drawing these conclusions it should be noted that insulin resistance varies between different demographic groups [29] therefore some individuals may require a greater reduction in fat intake and different dietary changes to experience similar effects. Nonetheless, it seems the overall recommendation for the general population should be that consuming a diet that adheres to UK recommendations of 35% energy from fat with less than 11% from SFA,  along with moderate intake of complex CHO and ensuring daily energy intake does not exceed expenditure, may be beneficial in maintaining insulin sensitivity and reducing risk of type 2 diabetes.

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